<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2026 Workiva-->
<!--r:aa3104ca-7531-42ed-8fd8-80a9cba6c759,g:bf640de4-8bba-46d9-acd5-de866ea51e1b-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member"/>
  <link:roleRef roleURI="http://www.blackdiamondtherapeutics.com/role/CoverPage" xlink:type="simple" xlink:href="bdtx-20260331.xsd#CoverPage"/>
  <link:definitionLink xlink:role="http://www.blackdiamondtherapeutics.com/role/CoverPage" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_DocumentInformationLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentInformationTable_019dce59-e823-7f53-875d-a883e8d588eb" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_DocumentInformationTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_DocumentInformationTable_019dce59-e823-7f53-875d-a883e8d588eb" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressesAddressTypeAxis_019dce59-e823-7be1-aa56-fbd61d5eea52" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityAddressesAddressTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_dei_DocumentInformationTable_019dce59-e823-7f53-875d-a883e8d588eb" xlink:to="loc_dei_EntityAddressesAddressTypeAxis_019dce59-e823-7be1-aa56-fbd61d5eea52" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_AddressTypeDomain_019dce59-e823-7be1-aa56-fbd61d5eea52_default" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_AddressTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_dei_EntityAddressesAddressTypeAxis_019dce59-e823-7be1-aa56-fbd61d5eea52" xlink:to="loc_dei_AddressTypeDomain_019dce59-e823-7be1-aa56-fbd61d5eea52_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_AddressTypeDomain_019dce59-e823-7a42-893d-0dbb500704d4" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_AddressTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_dei_EntityAddressesAddressTypeAxis_019dce59-e823-7be1-aa56-fbd61d5eea52" xlink:to="loc_dei_AddressTypeDomain_019dce59-e823-7a42-893d-0dbb500704d4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_FormerAddressMember_019dce59-e823-7bb7-b9e7-1ccd3000fd5c" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_FormerAddressMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_AddressTypeDomain_019dce59-e823-7a42-893d-0dbb500704d4" xlink:to="loc_dei_FormerAddressMember_019dce59-e823-7bb7-b9e7-1ccd3000fd5c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentType_5630f6fa-f73b-4b05-8275-9188a3b48f3b" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_DocumentType"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_DocumentType_5630f6fa-f73b-4b05-8275-9188a3b48f3b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentQuarterlyReport_7614db44-e782-41d2-8ccc-488687a854ad" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_DocumentQuarterlyReport"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_DocumentQuarterlyReport_7614db44-e782-41d2-8ccc-488687a854ad" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentPeriodEndDate_7100721e-a5c1-468a-9274-d3f470485ab5" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_DocumentPeriodEndDate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_DocumentPeriodEndDate_7100721e-a5c1-468a-9274-d3f470485ab5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentTransitionReport_ecbe38a6-5914-4971-8956-39a81e0a090b" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_DocumentTransitionReport"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_DocumentTransitionReport_ecbe38a6-5914-4971-8956-39a81e0a090b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityFileNumber_bb5d16a3-282d-40a9-897e-d1679efe5fb7" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityFileNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_EntityFileNumber_bb5d16a3-282d-40a9-897e-d1679efe5fb7" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityRegistrantName_112423e6-f9ab-4567-bb2b-efed96bd6390" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityRegistrantName"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_EntityRegistrantName_112423e6-f9ab-4567-bb2b-efed96bd6390" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityIncorporationStateCountryCode_8a2b53af-832f-401e-8d5a-325cd19000ab" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityIncorporationStateCountryCode"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_EntityIncorporationStateCountryCode_8a2b53af-832f-401e-8d5a-325cd19000ab" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityTaxIdentificationNumber_85a9a615-aa98-438f-967b-16e169db0a3a" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityTaxIdentificationNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_EntityTaxIdentificationNumber_85a9a615-aa98-438f-967b-16e169db0a3a" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressAddressLine1_be09d243-42da-46ff-9912-eef883e3db89" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityAddressAddressLine1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_EntityAddressAddressLine1_be09d243-42da-46ff-9912-eef883e3db89" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressCityOrTown_06c7f42d-3cc9-47af-a4d3-1d9ea52f4734" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityAddressCityOrTown"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_EntityAddressCityOrTown_06c7f42d-3cc9-47af-a4d3-1d9ea52f4734" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressStateOrProvince_a92bd381-8d7d-4d4d-a6a5-ee4bf5a98561" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityAddressStateOrProvince"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_EntityAddressStateOrProvince_a92bd381-8d7d-4d4d-a6a5-ee4bf5a98561" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressPostalZipCode_6227539b-3e2e-44c9-9edc-7791329774df" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityAddressPostalZipCode"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_EntityAddressPostalZipCode_6227539b-3e2e-44c9-9edc-7791329774df" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_CityAreaCode_bf0addce-a1d8-4477-940c-5c1419d94cec" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_CityAreaCode"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_CityAreaCode_bf0addce-a1d8-4477-940c-5c1419d94cec" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_LocalPhoneNumber_b016c947-67df-40ff-b69e-3d0281fe5646" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_LocalPhoneNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_LocalPhoneNumber_b016c947-67df-40ff-b69e-3d0281fe5646" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_Security12bTitle_ebae75e5-672d-4b60-b4a0-7a2359ae4b74" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_Security12bTitle"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_Security12bTitle_ebae75e5-672d-4b60-b4a0-7a2359ae4b74" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_TradingSymbol_e7fc3016-2ae7-4752-ab49-74c25da1e1ad" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_TradingSymbol"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_TradingSymbol_e7fc3016-2ae7-4752-ab49-74c25da1e1ad" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_SecurityExchangeName_92a9aebf-f2ff-447c-b960-4d4b81634186" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_SecurityExchangeName"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_SecurityExchangeName_92a9aebf-f2ff-447c-b960-4d4b81634186" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityCurrentReportingStatus_fe539c5f-77ec-43b0-8086-3345c6442c82" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityCurrentReportingStatus"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_EntityCurrentReportingStatus_fe539c5f-77ec-43b0-8086-3345c6442c82" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityInteractiveDataCurrent_6cccd6ca-6ce7-45b2-927e-79ecc5da52e0" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityInteractiveDataCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_EntityInteractiveDataCurrent_6cccd6ca-6ce7-45b2-927e-79ecc5da52e0" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityFilerCategory_6668b491-7fb9-4e69-be0a-5a7d7a8209fc" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityFilerCategory"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_EntityFilerCategory_6668b491-7fb9-4e69-be0a-5a7d7a8209fc" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntitySmallBusiness_5da65232-dfe3-4a4b-b61b-0047c9914a8e" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntitySmallBusiness"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_EntitySmallBusiness_5da65232-dfe3-4a4b-b61b-0047c9914a8e" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityEmergingGrowthCompany_9e5f9d28-6f75-4445-b585-5ff94ac66e5a" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityEmergingGrowthCompany"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_EntityEmergingGrowthCompany_9e5f9d28-6f75-4445-b585-5ff94ac66e5a" xlink:type="arc" order="21"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityShellCompany_d8417b5d-8ff7-4c0c-85be-468dd9b6951b" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityShellCompany"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_EntityShellCompany_d8417b5d-8ff7-4c0c-85be-468dd9b6951b" xlink:type="arc" order="22"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityCommonStockSharesOutstanding_7966a88f-3957-4ecd-b3f1-bfb72c0798e5" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityCommonStockSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_EntityCommonStockSharesOutstanding_7966a88f-3957-4ecd-b3f1-bfb72c0798e5" xlink:type="arc" order="23"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_AmendmentFlag_19a01b61-be7f-4cee-b28b-14d795f0d6ee" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_AmendmentFlag"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_AmendmentFlag_19a01b61-be7f-4cee-b28b-14d795f0d6ee" xlink:type="arc" order="24"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentFiscalPeriodFocus_955a8e96-a24b-4fb8-ae61-a884639130cd" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_DocumentFiscalPeriodFocus"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_DocumentFiscalPeriodFocus_955a8e96-a24b-4fb8-ae61-a884639130cd" xlink:type="arc" order="25"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentFiscalYearFocus_a402221e-5cb7-475c-8dc5-9c7868645f8b" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_DocumentFiscalYearFocus"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_DocumentFiscalYearFocus_a402221e-5cb7-475c-8dc5-9c7868645f8b" xlink:type="arc" order="26"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityCentralIndexKey_2c3bda80-c2df-451b-b317-2013cad26c37" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityCentralIndexKey"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_EntityCentralIndexKey_2c3bda80-c2df-451b-b317-2013cad26c37" xlink:type="arc" order="27"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_CurrentFiscalYearEndDate_605790ee-80c3-4fdd-a71d-3159eefd10cc" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_CurrentFiscalYearEndDate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019dce59-e823-7ead-95e6-bb77057343e7" xlink:to="loc_dei_CurrentFiscalYearEndDate_605790ee-80c3-4fdd-a71d-3159eefd10cc" xlink:type="arc" order="28"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.blackdiamondtherapeutics.com/role/CondensedConsolidatedStatementsofStockholdersEquityUnaudited" xlink:type="simple" xlink:href="bdtx-20260331.xsd#CondensedConsolidatedStatementsofStockholdersEquityUnaudited"/>
  <link:definitionLink xlink:role="http://www.blackdiamondtherapeutics.com/role/CondensedConsolidatedStatementsofStockholdersEquityUnaudited" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_8f4c8e3f-88af-464b-bc6b-885967105c09" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_e42b5345-f9ca-41c5-9a07-38d4c6f82a91" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_8f4c8e3f-88af-464b-bc6b-885967105c09" xlink:to="loc_us-gaap_StatementTable_e42b5345-f9ca-41c5-9a07-38d4c6f82a91" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_a4f70a47-650a-4098-9199-b5ba6e0b374c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_e42b5345-f9ca-41c5-9a07-38d4c6f82a91" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_a4f70a47-650a-4098-9199-b5ba6e0b374c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_a4f70a47-650a-4098-9199-b5ba6e0b374c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_a4f70a47-650a-4098-9199-b5ba6e0b374c" xlink:to="loc_us-gaap_EquityComponentDomain_a4f70a47-650a-4098-9199-b5ba6e0b374c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_f5bfb398-443b-4788-a61e-3d0924ad18da" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_a4f70a47-650a-4098-9199-b5ba6e0b374c" xlink:to="loc_us-gaap_EquityComponentDomain_f5bfb398-443b-4788-a61e-3d0924ad18da" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_983cd9ae-c0a3-4136-a49d-658e5cb93713" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_f5bfb398-443b-4788-a61e-3d0924ad18da" xlink:to="loc_us-gaap_CommonStockMember_983cd9ae-c0a3-4136-a49d-658e5cb93713" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalMember_78bda927-3eb8-4321-a9b9-7a1949d895de" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AdditionalPaidInCapitalMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_f5bfb398-443b-4788-a61e-3d0924ad18da" xlink:to="loc_us-gaap_AdditionalPaidInCapitalMember_78bda927-3eb8-4321-a9b9-7a1949d895de" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_e7b9f44b-94af-4dbf-8dd2-7a5c20d53036" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_f5bfb398-443b-4788-a61e-3d0924ad18da" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_e7b9f44b-94af-4dbf-8dd2-7a5c20d53036" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsMember_d44b8a9d-2dae-4644-a315-a614cd2ac106" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RetainedEarningsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_f5bfb398-443b-4788-a61e-3d0924ad18da" xlink:to="loc_us-gaap_RetainedEarningsMember_d44b8a9d-2dae-4644-a315-a614cd2ac106" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_7e3d5d94-7aac-4e76-9c42-1394993157c8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_8f4c8e3f-88af-464b-bc6b-885967105c09" xlink:to="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_7e3d5d94-7aac-4e76-9c42-1394993157c8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesOutstanding_848c4f3d-e476-4370-a2e1-c9dc0233b03f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_7e3d5d94-7aac-4e76-9c42-1394993157c8" xlink:to="loc_us-gaap_CommonStockSharesOutstanding_848c4f3d-e476-4370-a2e1-c9dc0233b03f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_fc9cf0f0-9ac3-47f2-9970-404155f1f129" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockholdersEquity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_7e3d5d94-7aac-4e76-9c42-1394993157c8" xlink:to="loc_us-gaap_StockholdersEquity_fc9cf0f0-9ac3-47f2-9970-404155f1f129" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_14f20c45-697b-40ea-8ed8-8ca43bc34340" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_7e3d5d94-7aac-4e76-9c42-1394993157c8" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_14f20c45-697b-40ea-8ed8-8ca43bc34340" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan_e51cfa3c-c032-4e1c-aebe-42bb816b8b81" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_7e3d5d94-7aac-4e76-9c42-1394993157c8" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan_e51cfa3c-c032-4e1c-aebe-42bb816b8b81" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardNetOfForfeitures_878758fd-3bc7-4cc4-a39a-e87d7a4876b2" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardNetOfForfeitures"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_7e3d5d94-7aac-4e76-9c42-1394993157c8" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardNetOfForfeitures_878758fd-3bc7-4cc4-a39a-e87d7a4876b2" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_b4fafc49-7005-43a4-8406-8eec88567f4d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_7e3d5d94-7aac-4e76-9c42-1394993157c8" xlink:to="loc_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_b4fafc49-7005-43a4-8406-8eec88567f4d" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation_7e275608-a10a-441a-b4ff-99813ac7a944" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_7e3d5d94-7aac-4e76-9c42-1394993157c8" xlink:to="loc_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation_7e275608-a10a-441a-b4ff-99813ac7a944" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_c7777718-99ff-4b89-877a-3d7f6c4b68f1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_7e3d5d94-7aac-4e76-9c42-1394993157c8" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_c7777718-99ff-4b89-877a-3d7f6c4b68f1" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_f61f128a-bae0-4f1a-8883-a19638f1c45d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_7e3d5d94-7aac-4e76-9c42-1394993157c8" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_f61f128a-bae0-4f1a-8883-a19638f1c45d" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentBeforeReclassificationAdjustmentsNetOfTax_5b826160-c677-47dd-a1f1-cb7cba3c304b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentBeforeReclassificationAdjustmentsNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_7e3d5d94-7aac-4e76-9c42-1394993157c8" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentBeforeReclassificationAdjustmentsNetOfTax_5b826160-c677-47dd-a1f1-cb7cba3c304b" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_1ae9bf3c-754b-488d-943f-44a97e082e2a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_7e3d5d94-7aac-4e76-9c42-1394993157c8" xlink:to="loc_us-gaap_NetIncomeLoss_1ae9bf3c-754b-488d-943f-44a97e082e2a" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesOutstanding_05739504-5f0b-46e8-80be-5f5cf7489b9c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockSharesOutstanding"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_ba34cc01-a787-4d93-a172-d474049a6c10" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockholdersEquity"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.blackdiamondtherapeutics.com/role/NATUREOFBUSINESSANDBASISOFPRESENTATIONDetails" xlink:type="simple" xlink:href="bdtx-20260331.xsd#NATUREOFBUSINESSANDBASISOFPRESENTATIONDetails"/>
  <link:definitionLink xlink:role="http://www.blackdiamondtherapeutics.com/role/NATUREOFBUSINESSANDBASISOFPRESENTATIONDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockLineItems_5a7009d3-15bf-4e70-ade7-cdedaff9f718" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SubsidiarySaleOfStockLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_cd61bb46-fae0-4c2a-b21c-cc4e832c4037" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_5a7009d3-15bf-4e70-ade7-cdedaff9f718" xlink:to="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_cd61bb46-fae0-4c2a-b21c-cc4e832c4037" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_7ae4327c-39c4-4fe0-aae9-6ba7cf3d212e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_cd61bb46-fae0-4c2a-b21c-cc4e832c4037" xlink:to="loc_us-gaap_TypeOfArrangementAxis_7ae4327c-39c4-4fe0-aae9-6ba7cf3d212e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_7ae4327c-39c4-4fe0-aae9-6ba7cf3d212e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_7ae4327c-39c4-4fe0-aae9-6ba7cf3d212e" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_7ae4327c-39c4-4fe0-aae9-6ba7cf3d212e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_d16988a6-c4b7-438f-8d0d-c8e43b512111" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_7ae4327c-39c4-4fe0-aae9-6ba7cf3d212e" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_d16988a6-c4b7-438f-8d0d-c8e43b512111" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_ServierAgreementMember_3c455187-1a4a-47a7-97eb-e64e50699835" xlink:href="bdtx-20260331.xsd#bdtx_ServierAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_d16988a6-c4b7-438f-8d0d-c8e43b512111" xlink:to="loc_bdtx_ServierAgreementMember_3c455187-1a4a-47a7-97eb-e64e50699835" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockAxis_019d418b-40e9-7136-8038-4e02a9d656a6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SubsidiarySaleOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_cd61bb46-fae0-4c2a-b21c-cc4e832c4037" xlink:to="loc_us-gaap_SubsidiarySaleOfStockAxis_019d418b-40e9-7136-8038-4e02a9d656a6" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_019d418b-40e9-7136-8038-4e02a9d656a6_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_019d418b-40e9-7136-8038-4e02a9d656a6" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_019d418b-40e9-7136-8038-4e02a9d656a6_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_019d418b-40e9-7d96-9e43-10418c79ce56" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_019d418b-40e9-7136-8038-4e02a9d656a6" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_019d418b-40e9-7d96-9e43-10418c79ce56" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_ShelfRegistrationStatementMember_019d418b-40e9-74f6-9fab-c6cdb6489f45" xlink:href="bdtx-20260331.xsd#bdtx_ShelfRegistrationStatementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_019d418b-40e9-7d96-9e43-10418c79ce56" xlink:to="loc_bdtx_ShelfRegistrationStatementMember_019d418b-40e9-74f6-9fab-c6cdb6489f45" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_OpenMarketSaleMember_019d418b-40e9-7b83-b5dc-dde1b15e04a8" xlink:href="bdtx-20260331.xsd#bdtx_OpenMarketSaleMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_019d418b-40e9-7d96-9e43-10418c79ce56" xlink:to="loc_bdtx_OpenMarketSaleMember_019d418b-40e9-7b83-b5dc-dde1b15e04a8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_AtMarketEquityProgramMember_019d418b-40e9-74df-917f-cc4083944e6f" xlink:href="bdtx-20260331.xsd#bdtx_AtMarketEquityProgramMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_019d418b-40e9-7d96-9e43-10418c79ce56" xlink:to="loc_bdtx_AtMarketEquityProgramMember_019d418b-40e9-74df-917f-cc4083944e6f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_CollaborativeArrangementUpfrontPayment_1eb78401-bbd9-4f98-a772-1c5ca4f5d92b" xlink:href="bdtx-20260331.xsd#bdtx_CollaborativeArrangementUpfrontPayment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_5a7009d3-15bf-4e70-ade7-cdedaff9f718" xlink:to="loc_bdtx_CollaborativeArrangementUpfrontPayment_1eb78401-bbd9-4f98-a772-1c5ca4f5d92b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_CollaborativeArrangementMilestonePayments_474cea15-571f-4588-b4fb-9eb79bb8e9d5" xlink:href="bdtx-20260331.xsd#bdtx_CollaborativeArrangementMilestonePayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_5a7009d3-15bf-4e70-ade7-cdedaff9f718" xlink:to="loc_bdtx_CollaborativeArrangementMilestonePayments_474cea15-571f-4588-b4fb-9eb79bb8e9d5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_SaleOfStockAuthorizedConsideration_019d418b-40e9-787d-bee6-4209ff2dc420" xlink:href="bdtx-20260331.xsd#bdtx_SaleOfStockAuthorizedConsideration"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_5a7009d3-15bf-4e70-ade7-cdedaff9f718" xlink:to="loc_bdtx_SaleOfStockAuthorizedConsideration_019d418b-40e9-787d-bee6-4209ff2dc420" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_019d418b-40e9-781e-b39b-3889c9e4edf6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_5a7009d3-15bf-4e70-ade7-cdedaff9f718" xlink:to="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_019d418b-40e9-781e-b39b-3889c9e4edf6" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueNewIssues_019d418b-40e9-791f-b1d2-e2bc27532bdc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_5a7009d3-15bf-4e70-ade7-cdedaff9f718" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueNewIssues_019d418b-40e9-791f-b1d2-e2bc27532bdc" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_019d418b-40e9-7117-a793-9a5bfd3f02d1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SaleOfStockConsiderationReceivedOnTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_5a7009d3-15bf-4e70-ade7-cdedaff9f718" xlink:to="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_019d418b-40e9-7117-a793-9a5bfd3f02d1" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsAccumulatedDeficit_72dcc914-f5a4-456c-8fdd-1ff87da94b9a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RetainedEarningsAccumulatedDeficit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_5a7009d3-15bf-4e70-ade7-cdedaff9f718" xlink:to="loc_us-gaap_RetainedEarningsAccumulatedDeficit_72dcc914-f5a4-456c-8fdd-1ff87da94b9a" xlink:type="arc" order="6"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.blackdiamondtherapeutics.com/role/FAIRVALUEMEASUREMENTSDetails" xlink:type="simple" xlink:href="bdtx-20260331.xsd#FAIRVALUEMEASUREMENTSDetails"/>
  <link:definitionLink xlink:role="http://www.blackdiamondtherapeutics.com/role/FAIRVALUEMEASUREMENTSDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_e97ca72c-82b0-4841-b077-aa743c8356dd" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_21042d50-2bdf-4b05-8705-b57f9712b3b2" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_e97ca72c-82b0-4841-b077-aa743c8356dd" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_21042d50-2bdf-4b05-8705-b57f9712b3b2" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAxis_019d4196-7826-767f-82b4-fed080eff470" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CashAndCashEquivalentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_21042d50-2bdf-4b05-8705-b57f9712b3b2" xlink:to="loc_us-gaap_CashAndCashEquivalentsAxis_019d4196-7826-767f-82b4-fed080eff470" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_019d4196-7826-767f-82b4-fed080eff470_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_CashAndCashEquivalentsAxis_019d4196-7826-767f-82b4-fed080eff470" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_019d4196-7826-767f-82b4-fed080eff470_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_019d4196-7826-77f8-9e47-94cff964e77f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_CashAndCashEquivalentsAxis_019d4196-7826-767f-82b4-fed080eff470" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_019d4196-7826-77f8-9e47-94cff964e77f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MoneyMarketFundsMember_701c360f-a774-4d8b-93c6-7bc6d2aa875e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_MoneyMarketFundsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_019d4196-7826-77f8-9e47-94cff964e77f" xlink:to="loc_us-gaap_MoneyMarketFundsMember_701c360f-a774-4d8b-93c6-7bc6d2aa875e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_7795dd0a-55e1-4970-a6f2-0d1b23d5b9d4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_21042d50-2bdf-4b05-8705-b57f9712b3b2" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_7795dd0a-55e1-4970-a6f2-0d1b23d5b9d4" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_7795dd0a-55e1-4970-a6f2-0d1b23d5b9d4_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_7795dd0a-55e1-4970-a6f2-0d1b23d5b9d4" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_7795dd0a-55e1-4970-a6f2-0d1b23d5b9d4_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_1fd7ba51-898a-4f0c-8bbd-30a5025d7493" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_7795dd0a-55e1-4970-a6f2-0d1b23d5b9d4" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_1fd7ba51-898a-4f0c-8bbd-30a5025d7493" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel1Member_3c49a1c8-8874-422e-b59d-0a80635eae7a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueInputsLevel1Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_1fd7ba51-898a-4f0c-8bbd-30a5025d7493" xlink:to="loc_us-gaap_FairValueInputsLevel1Member_3c49a1c8-8874-422e-b59d-0a80635eae7a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_26747b38-d277-4916-bc7f-6effe864c85e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueInputsLevel2Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_1fd7ba51-898a-4f0c-8bbd-30a5025d7493" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_26747b38-d277-4916-bc7f-6effe864c85e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel3Member_155e30aa-d76a-4ae1-80ac-6ae3cc37152e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueInputsLevel3Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_1fd7ba51-898a-4f0c-8bbd-30a5025d7493" xlink:to="loc_us-gaap_FairValueInputsLevel3Member_155e30aa-d76a-4ae1-80ac-6ae3cc37152e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_9c40353d-9989-4873-8148-1e2ca3e4e112" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_21042d50-2bdf-4b05-8705-b57f9712b3b2" xlink:to="loc_us-gaap_FinancialInstrumentAxis_9c40353d-9989-4873-8148-1e2ca3e4e112" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_9c40353d-9989-4873-8148-1e2ca3e4e112_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_9c40353d-9989-4873-8148-1e2ca3e4e112" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_9c40353d-9989-4873-8148-1e2ca3e4e112_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_68fe736e-dd4d-4c63-bc0a-adafa7154042" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_9c40353d-9989-4873-8148-1e2ca3e4e112" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_68fe736e-dd4d-4c63-bc0a-adafa7154042" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommercialPaperNotIncludedWithCashAndCashEquivalentsMember_6c7969b1-0a6a-461d-be48-09d23e09805b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommercialPaperNotIncludedWithCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_68fe736e-dd4d-4c63-bc0a-adafa7154042" xlink:to="loc_us-gaap_CommercialPaperNotIncludedWithCashAndCashEquivalentsMember_6c7969b1-0a6a-461d-be48-09d23e09805b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CorporateBondSecuritiesMember_73245ba7-41e4-4e01-bdf0-2da6b6d7ac99" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CorporateBondSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_68fe736e-dd4d-4c63-bc0a-adafa7154042" xlink:to="loc_us-gaap_CorporateBondSecuritiesMember_73245ba7-41e4-4e01-bdf0-2da6b6d7ac99" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentAgenciesDebtSecuritiesMember_03606a96-fed4-44a4-a796-98f14ff9c90d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_USGovernmentAgenciesDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_68fe736e-dd4d-4c63-bc0a-adafa7154042" xlink:to="loc_us-gaap_USGovernmentAgenciesDebtSecuritiesMember_03606a96-fed4-44a4-a796-98f14ff9c90d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosureAbstract_42e32f12-3184-4764-85b0-b33a7f270c2a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetsFairValueDisclosureAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_e97ca72c-82b0-4841-b077-aa743c8356dd" xlink:to="loc_us-gaap_AssetsFairValueDisclosureAbstract_42e32f12-3184-4764-85b0-b33a7f270c2a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_403f7fb0-c98b-4113-85c6-244e46dac08d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_42e32f12-3184-4764-85b0-b33a7f270c2a" xlink:to="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_403f7fb0-c98b-4113-85c6-244e46dac08d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentsFairValueDisclosure_6f36e1f5-2887-4df5-a44c-00d1eeb910df" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_InvestmentsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_42e32f12-3184-4764-85b0-b33a7f270c2a" xlink:to="loc_us-gaap_InvestmentsFairValueDisclosure_6f36e1f5-2887-4df5-a44c-00d1eeb910df" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_f73c8236-173f-4989-9f2d-8b6af3c1cb5a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_42e32f12-3184-4764-85b0-b33a7f270c2a" xlink:to="loc_us-gaap_AssetsFairValueDisclosure_f73c8236-173f-4989-9f2d-8b6af3c1cb5a" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.blackdiamondtherapeutics.com/role/INVESTMENTSScheduleofMarketableSecuritiesDetails" xlink:type="simple" xlink:href="bdtx-20260331.xsd#INVESTMENTSScheduleofMarketableSecuritiesDetails"/>
  <link:definitionLink xlink:role="http://www.blackdiamondtherapeutics.com/role/INVESTMENTSScheduleofMarketableSecuritiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_cc87bd19-8be7-4e7e-9c5b-84c14f4d9042" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_00341214-494c-4b24-9849-62daaaf69d3a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DebtSecuritiesAvailableForSaleTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_cc87bd19-8be7-4e7e-9c5b-84c14f4d9042" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_00341214-494c-4b24-9849-62daaaf69d3a" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_013bd93e-02a7-43d7-a8fb-8646212c5f04" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_00341214-494c-4b24-9849-62daaaf69d3a" xlink:to="loc_us-gaap_FinancialInstrumentAxis_013bd93e-02a7-43d7-a8fb-8646212c5f04" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_013bd93e-02a7-43d7-a8fb-8646212c5f04_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_013bd93e-02a7-43d7-a8fb-8646212c5f04" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_013bd93e-02a7-43d7-a8fb-8646212c5f04_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_92fba6ee-762c-48a2-bfd1-ba2fb486b9b6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_013bd93e-02a7-43d7-a8fb-8646212c5f04" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_92fba6ee-762c-48a2-bfd1-ba2fb486b9b6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommercialPaperNotIncludedWithCashAndCashEquivalentsMember_b1e0a90f-0058-4d47-8e98-7a9edbc1a5ae" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommercialPaperNotIncludedWithCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_92fba6ee-762c-48a2-bfd1-ba2fb486b9b6" xlink:to="loc_us-gaap_CommercialPaperNotIncludedWithCashAndCashEquivalentsMember_b1e0a90f-0058-4d47-8e98-7a9edbc1a5ae" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CorporateBondSecuritiesMember_ea759207-6acf-4583-861a-ed66900ba9f9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CorporateBondSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_92fba6ee-762c-48a2-bfd1-ba2fb486b9b6" xlink:to="loc_us-gaap_CorporateBondSecuritiesMember_ea759207-6acf-4583-861a-ed66900ba9f9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentAgenciesDebtSecuritiesMember_80ec489f-45c3-4387-8c0f-1aaeb18c9a4f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_USGovernmentAgenciesDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_92fba6ee-762c-48a2-bfd1-ba2fb486b9b6" xlink:to="loc_us-gaap_USGovernmentAgenciesDebtSecuritiesMember_80ec489f-45c3-4387-8c0f-1aaeb18c9a4f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_96465d89-fb0a-4a20-abe6-f9c7e3d6fe40" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_cc87bd19-8be7-4e7e-9c5b-84c14f4d9042" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_96465d89-fb0a-4a20-abe6-f9c7e3d6fe40" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_02dcee2a-0d33-457c-bca9-8ad778a24dbe" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_cc87bd19-8be7-4e7e-9c5b-84c14f4d9042" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_02dcee2a-0d33-457c-bca9-8ad778a24dbe" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_8eacab7e-59e5-4af3-bc45-4de948720bd6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_cc87bd19-8be7-4e7e-9c5b-84c14f4d9042" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_8eacab7e-59e5-4af3-bc45-4de948720bd6" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_88c30104-0c63-4b87-8f1e-2a70959f4216" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_cc87bd19-8be7-4e7e-9c5b-84c14f4d9042" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_88c30104-0c63-4b87-8f1e-2a70959f4216" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.blackdiamondtherapeutics.com/role/PROPERTYANDEQUIPMENTDetails" xlink:type="simple" xlink:href="bdtx-20260331.xsd#PROPERTYANDEQUIPMENTDetails"/>
  <link:definitionLink xlink:role="http://www.blackdiamondtherapeutics.com/role/PROPERTYANDEQUIPMENTDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentLineItems_29888ed4-caa9-4f04-8646-f3b6dae33937" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PropertyPlantAndEquipmentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_8df38be8-47fa-4273-86ea-31bccb334a74" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfPropertyPlantAndEquipmentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_29888ed4-caa9-4f04-8646-f3b6dae33937" xlink:to="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_8df38be8-47fa-4273-86ea-31bccb334a74" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_906171fe-1a1b-4372-b906-5911fc2de3a9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_8df38be8-47fa-4273-86ea-31bccb334a74" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_906171fe-1a1b-4372-b906-5911fc2de3a9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_906171fe-1a1b-4372-b906-5911fc2de3a9_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_906171fe-1a1b-4372-b906-5911fc2de3a9" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_906171fe-1a1b-4372-b906-5911fc2de3a9_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_6d3393fe-cc00-475e-aa90-08d73c74aa89" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_906171fe-1a1b-4372-b906-5911fc2de3a9" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_6d3393fe-cc00-475e-aa90-08d73c74aa89" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LeaseholdImprovementsMember_e904ddc1-faa2-4fcd-8fdd-f461549860b0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LeaseholdImprovementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_6d3393fe-cc00-475e-aa90-08d73c74aa89" xlink:to="loc_us-gaap_LeaseholdImprovementsMember_e904ddc1-faa2-4fcd-8fdd-f461549860b0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentGross_c6b173e8-5f89-4bb3-a506-935b02052d74" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PropertyPlantAndEquipmentGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_29888ed4-caa9-4f04-8646-f3b6dae33937" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentGross_c6b173e8-5f89-4bb3-a506-935b02052d74" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_bb0651fb-2f29-44e8-a760-d9dffb63f034" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_29888ed4-caa9-4f04-8646-f3b6dae33937" xlink:to="loc_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_bb0651fb-2f29-44e8-a760-d9dffb63f034" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentNet_67ad0900-5f9a-4ab4-b02b-cfdd34ee7091" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_29888ed4-caa9-4f04-8646-f3b6dae33937" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentNet_67ad0900-5f9a-4ab4-b02b-cfdd34ee7091" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Depreciation_7f078e5b-6f3d-46b5-b479-58f86adf62e3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_Depreciation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_29888ed4-caa9-4f04-8646-f3b6dae33937" xlink:to="loc_us-gaap_Depreciation_7f078e5b-6f3d-46b5-b479-58f86adf62e3" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.blackdiamondtherapeutics.com/role/EQUITYMETHODINVESTMENTDetails" xlink:type="simple" xlink:href="bdtx-20260331.xsd#EQUITYMETHODINVESTMENTDetails"/>
  <link:definitionLink xlink:role="http://www.blackdiamondtherapeutics.com/role/EQUITYMETHODINVESTMENTDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEquityMethodInvestmentsLineItems_4f1efe58-8bcd-49fb-8af2-cb1598159310" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfEquityMethodInvestmentsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEquityMethodInvestmentsTable_37131733-82a7-411a-b8fb-3e98fad5fd56" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfEquityMethodInvestmentsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfEquityMethodInvestmentsLineItems_4f1efe58-8bcd-49fb-8af2-cb1598159310" xlink:to="loc_us-gaap_ScheduleOfEquityMethodInvestmentsTable_37131733-82a7-411a-b8fb-3e98fad5fd56" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_6cea8f5a-058f-485f-93dc-e3c06ea1301e" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEquityMethodInvestmentsTable_37131733-82a7-411a-b8fb-3e98fad5fd56" xlink:to="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_6cea8f5a-058f-485f-93dc-e3c06ea1301e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_6cea8f5a-058f-485f-93dc-e3c06ea1301e_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_EquityMethodInvesteeNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_6cea8f5a-058f-485f-93dc-e3c06ea1301e" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_6cea8f5a-058f-485f-93dc-e3c06ea1301e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_d7681b5e-9fce-405c-8373-2b6e3b2e93b3" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_EquityMethodInvesteeNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_6cea8f5a-058f-485f-93dc-e3c06ea1301e" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_d7681b5e-9fce-405c-8373-2b6e3b2e93b3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_RevelioTherapeuticsIncMember_912b7b3f-f5a0-4067-945d-27d27520d7a3" xlink:href="bdtx-20260331.xsd#bdtx_RevelioTherapeuticsIncMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_d7681b5e-9fce-405c-8373-2b6e3b2e93b3" xlink:to="loc_bdtx_RevelioTherapeuticsIncMember_912b7b3f-f5a0-4067-945d-27d27520d7a3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_EquityMethodInvestmentSharesReceivedInNoncashExchange_f5e5aa4a-bf47-4cc2-8401-978bdb72007f" xlink:href="bdtx-20260331.xsd#bdtx_EquityMethodInvestmentSharesReceivedInNoncashExchange"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfEquityMethodInvestmentsLineItems_4f1efe58-8bcd-49fb-8af2-cb1598159310" xlink:to="loc_bdtx_EquityMethodInvestmentSharesReceivedInNoncashExchange_f5e5aa4a-bf47-4cc2-8401-978bdb72007f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestmentOwnershipPercentage_8c029ddd-c87c-4c6d-a21d-780d38250698" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EquityMethodInvestmentOwnershipPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfEquityMethodInvestmentsLineItems_4f1efe58-8bcd-49fb-8af2-cb1598159310" xlink:to="loc_us-gaap_EquityMethodInvestmentOwnershipPercentage_8c029ddd-c87c-4c6d-a21d-780d38250698" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestments_e816c225-91ee-45b3-9100-f071f2ab82c1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EquityMethodInvestments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfEquityMethodInvestmentsLineItems_4f1efe58-8bcd-49fb-8af2-cb1598159310" xlink:to="loc_us-gaap_EquityMethodInvestments_e816c225-91ee-45b3-9100-f071f2ab82c1" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.blackdiamondtherapeutics.com/role/STOCKBASEDCOMPENSATIONNarrativeDetails" xlink:type="simple" xlink:href="bdtx-20260331.xsd#STOCKBASEDCOMPENSATIONNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.blackdiamondtherapeutics.com/role/STOCKBASEDCOMPENSATIONNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_089f43f8-6058-4c76-a714-ddf9c8ffe59b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_8d2d83c9-2c9c-44cf-a18a-80806d2d432c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_089f43f8-6058-4c76-a714-ddf9c8ffe59b" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_8d2d83c9-2c9c-44cf-a18a-80806d2d432c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_af007a64-f2c6-4196-b6fd-e3c1eaab15aa" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_8d2d83c9-2c9c-44cf-a18a-80806d2d432c" xlink:to="loc_us-gaap_PlanNameAxis_af007a64-f2c6-4196-b6fd-e3c1eaab15aa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_af007a64-f2c6-4196-b6fd-e3c1eaab15aa_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_af007a64-f2c6-4196-b6fd-e3c1eaab15aa" xlink:to="loc_us-gaap_PlanNameDomain_af007a64-f2c6-4196-b6fd-e3c1eaab15aa_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_f891dc33-1498-49c3-b53f-80a8e504b55e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_af007a64-f2c6-4196-b6fd-e3c1eaab15aa" xlink:to="loc_us-gaap_PlanNameDomain_f891dc33-1498-49c3-b53f-80a8e504b55e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_A2020PlanMember_1cff4854-3e4b-4e0a-84fe-632384ea488b" xlink:href="bdtx-20260331.xsd#bdtx_A2020PlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_f891dc33-1498-49c3-b53f-80a8e504b55e" xlink:to="loc_bdtx_A2020PlanMember_1cff4854-3e4b-4e0a-84fe-632384ea488b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_A2020EmployeeStockPurchasePlanMember_0f536480-4e96-477d-aafa-4cc4ee0ed782" xlink:href="bdtx-20260331.xsd#bdtx_A2020EmployeeStockPurchasePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_f891dc33-1498-49c3-b53f-80a8e504b55e" xlink:to="loc_bdtx_A2020EmployeeStockPurchasePlanMember_0f536480-4e96-477d-aafa-4cc4ee0ed782" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_259917be-2f92-4464-a78a-c1215c2e12f9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_8d2d83c9-2c9c-44cf-a18a-80806d2d432c" xlink:to="loc_us-gaap_AwardTypeAxis_259917be-2f92-4464-a78a-c1215c2e12f9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_259917be-2f92-4464-a78a-c1215c2e12f9_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_259917be-2f92-4464-a78a-c1215c2e12f9" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_259917be-2f92-4464-a78a-c1215c2e12f9_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_6f2ef76e-4b3a-4689-a9b4-65354e493d32" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_259917be-2f92-4464-a78a-c1215c2e12f9" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_6f2ef76e-4b3a-4689-a9b4-65354e493d32" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_36c25dc4-72b9-42fd-a7ea-49cfe91acc06" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_6f2ef76e-4b3a-4689-a9b4-65354e493d32" xlink:to="loc_us-gaap_EmployeeStockOptionMember_36c25dc4-72b9-42fd-a7ea-49cfe91acc06" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_753a696d-4e73-4e1f-af5d-9555c43e3b9f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_6f2ef76e-4b3a-4689-a9b4-65354e493d32" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_753a696d-4e73-4e1f-af5d-9555c43e3b9f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GranteeStatusAxis_019d41b1-cd6d-7e9c-913a-e99d667f2ce5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_GranteeStatusAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_8d2d83c9-2c9c-44cf-a18a-80806d2d432c" xlink:to="loc_us-gaap_GranteeStatusAxis_019d41b1-cd6d-7e9c-913a-e99d667f2ce5" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GranteeStatusDomain_019d41b1-cd6d-7e9c-913a-e99d667f2ce5_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_GranteeStatusDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_GranteeStatusAxis_019d41b1-cd6d-7e9c-913a-e99d667f2ce5" xlink:to="loc_us-gaap_GranteeStatusDomain_019d41b1-cd6d-7e9c-913a-e99d667f2ce5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GranteeStatusDomain_019d41b1-cd6d-7e54-88e4-66fa5a5a15dc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_GranteeStatusDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_GranteeStatusAxis_019d41b1-cd6d-7e9c-913a-e99d667f2ce5" xlink:to="loc_us-gaap_GranteeStatusDomain_019d41b1-cd6d-7e54-88e4-66fa5a5a15dc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedPaymentArrangementNonemployeeMember_019d41b1-cd6e-7fe5-84f6-86384fc0f1cb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedPaymentArrangementNonemployeeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_GranteeStatusDomain_019d41b1-cd6d-7e54-88e4-66fa5a5a15dc" xlink:to="loc_us-gaap_ShareBasedPaymentArrangementNonemployeeMember_019d41b1-cd6e-7fe5-84f6-86384fc0f1cb" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_ShareBasedCompensationArrangementByShareBasedPaymentAwardAnnualIncreaseOfAuthorizedSharesPercentOfCommonStockOutstanding_d71373ab-f922-4565-bdd1-c55d8e028461" xlink:href="bdtx-20260331.xsd#bdtx_ShareBasedCompensationArrangementByShareBasedPaymentAwardAnnualIncreaseOfAuthorizedSharesPercentOfCommonStockOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_089f43f8-6058-4c76-a714-ddf9c8ffe59b" xlink:to="loc_bdtx_ShareBasedCompensationArrangementByShareBasedPaymentAwardAnnualIncreaseOfAuthorizedSharesPercentOfCommonStockOutstanding_d71373ab-f922-4565-bdd1-c55d8e028461" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized_493017a8-a5a3-44f6-8b10-1a925745bb2f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_089f43f8-6058-4c76-a714-ddf9c8ffe59b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized_493017a8-a5a3-44f6-8b10-1a925745bb2f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesIssuedInPeriod_8581f98f-7133-4e5a-958b-3cd50c24c960" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesIssuedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_089f43f8-6058-4c76-a714-ddf9c8ffe59b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesIssuedInPeriod_8581f98f-7133-4e5a-958b-3cd50c24c960" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_50fdee07-ab95-435d-b341-bdc27d943924" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_089f43f8-6058-4c76-a714-ddf9c8ffe59b" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_50fdee07-ab95-435d-b341-bdc27d943924" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_3e37363c-ff30-4901-a89f-230cddab5ad0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_089f43f8-6058-4c76-a714-ddf9c8ffe59b" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_3e37363c-ff30-4901-a89f-230cddab5ad0" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodTotalFairValue_9c2ab899-a30d-4331-bd23-83a7a3df189b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodTotalFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_089f43f8-6058-4c76-a714-ddf9c8ffe59b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodTotalFairValue_9c2ab899-a30d-4331-bd23-83a7a3df189b" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_3dacf449-0ac8-47b0-958d-c3f286b83e7b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_089f43f8-6058-4c76-a714-ddf9c8ffe59b" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_3dacf449-0ac8-47b0-958d-c3f286b83e7b" xlink:type="arc" order="6"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.blackdiamondtherapeutics.com/role/STOCKBASEDCOMPENSATIONScheduleofStockBasedCompensationDetails" xlink:type="simple" xlink:href="bdtx-20260331.xsd#STOCKBASEDCOMPENSATIONScheduleofStockBasedCompensationDetails"/>
  <link:definitionLink xlink:role="http://www.blackdiamondtherapeutics.com/role/STOCKBASEDCOMPENSATIONScheduleofStockBasedCompensationDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_e96204e9-9ee3-4ee7-86b3-94c687e65a3d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_0c935878-0ea5-41c5-b900-1c361bd23be7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_e96204e9-9ee3-4ee7-86b3-94c687e65a3d" xlink:to="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_0c935878-0ea5-41c5-b900-1c361bd23be7" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_3e9d9be3-515c-41cc-9ead-a5604d157637" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_0c935878-0ea5-41c5-b900-1c361bd23be7" xlink:to="loc_us-gaap_AwardTypeAxis_3e9d9be3-515c-41cc-9ead-a5604d157637" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_3e9d9be3-515c-41cc-9ead-a5604d157637_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_3e9d9be3-515c-41cc-9ead-a5604d157637" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_3e9d9be3-515c-41cc-9ead-a5604d157637_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_822f94ed-4710-4bbd-8151-3423f4800f21" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_3e9d9be3-515c-41cc-9ead-a5604d157637" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_822f94ed-4710-4bbd-8151-3423f4800f21" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_6fab21fb-2f17-4173-93ee-420c29be7fb4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_822f94ed-4710-4bbd-8151-3423f4800f21" xlink:to="loc_us-gaap_EmployeeStockOptionMember_6fab21fb-2f17-4173-93ee-420c29be7fb4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_1612149b-6b08-4e37-8d79-8065d8c4d164" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_822f94ed-4710-4bbd-8151-3423f4800f21" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_1612149b-6b08-4e37-8d79-8065d8c4d164" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_OtherAwardTypeMember_e156e409-f65b-455f-9973-de7093c50dfb" xlink:href="bdtx-20260331.xsd#bdtx_OtherAwardTypeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_822f94ed-4710-4bbd-8151-3423f4800f21" xlink:to="loc_bdtx_OtherAwardTypeMember_e156e409-f65b-455f-9973-de7093c50dfb" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_4c6a4888-3a14-4505-921b-7ae05439759e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeStatementLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_0c935878-0ea5-41c5-b900-1c361bd23be7" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_4c6a4888-3a14-4505-921b-7ae05439759e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_4c6a4888-3a14-4505-921b-7ae05439759e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_4c6a4888-3a14-4505-921b-7ae05439759e" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_4c6a4888-3a14-4505-921b-7ae05439759e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_19c18361-5827-4ef2-b108-3b70297997ee" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_4c6a4888-3a14-4505-921b-7ae05439759e" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_19c18361-5827-4ef2-b108-3b70297997ee" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpenseMember_3f6e9ebe-3b91-4e17-8978-6e35f21c2048" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_19c18361-5827-4ef2-b108-3b70297997ee" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpenseMember_3f6e9ebe-3b91-4e17-8978-6e35f21c2048" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpenseMember_f616a72b-454f-413b-935c-8bcdc2d41507" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_GeneralAndAdministrativeExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_19c18361-5827-4ef2-b108-3b70297997ee" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpenseMember_f616a72b-454f-413b-935c-8bcdc2d41507" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_a1b51614-a89e-4a71-83e4-e8813df29248" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_e96204e9-9ee3-4ee7-86b3-94c687e65a3d" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_a1b51614-a89e-4a71-83e4-e8813df29248" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.blackdiamondtherapeutics.com/role/STOCKBASEDCOMPENSATIONScheduleofRestrictedStockActivityDetails" xlink:type="simple" xlink:href="bdtx-20260331.xsd#STOCKBASEDCOMPENSATIONScheduleofRestrictedStockActivityDetails"/>
  <link:definitionLink xlink:role="http://www.blackdiamondtherapeutics.com/role/STOCKBASEDCOMPENSATIONScheduleofRestrictedStockActivityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01999b17-51cf-44c4-8b74-4dc3e2d029ee" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_5660f41a-c11b-4dbd-9a2b-a6dc04e1dd01" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01999b17-51cf-44c4-8b74-4dc3e2d029ee" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_5660f41a-c11b-4dbd-9a2b-a6dc04e1dd01" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_b22e55c4-9c1c-441c-ba22-30a5f1ff4652" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_5660f41a-c11b-4dbd-9a2b-a6dc04e1dd01" xlink:to="loc_us-gaap_AwardTypeAxis_b22e55c4-9c1c-441c-ba22-30a5f1ff4652" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_b22e55c4-9c1c-441c-ba22-30a5f1ff4652_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_b22e55c4-9c1c-441c-ba22-30a5f1ff4652" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_b22e55c4-9c1c-441c-ba22-30a5f1ff4652_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_5a0749ca-7c52-4ac5-81e8-7b2f08fc6db7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_b22e55c4-9c1c-441c-ba22-30a5f1ff4652" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_5a0749ca-7c52-4ac5-81e8-7b2f08fc6db7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_019d641b-4e7c-709f-8843-5bd7ef54055a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_5a0749ca-7c52-4ac5-81e8-7b2f08fc6db7" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_019d641b-4e7c-709f-8843-5bd7ef54055a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_8efd96a9-b6b4-40fd-a290-7de78adc72e8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01999b17-51cf-44c4-8b74-4dc3e2d029ee" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_8efd96a9-b6b4-40fd-a290-7de78adc72e8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_3a199ec3-82e2-4e80-9866-906e8bbff058" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_8efd96a9-b6b4-40fd-a290-7de78adc72e8" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_3a199ec3-82e2-4e80-9866-906e8bbff058" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_a472b40d-a02b-45ae-946f-301c7d39ebbf" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_8efd96a9-b6b4-40fd-a290-7de78adc72e8" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_a472b40d-a02b-45ae-946f-301c7d39ebbf" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_dd193ed6-fac7-41ed-876e-7ac3c9118a22" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_0c3cae9a-e5c6-4678-85df-7ed6c57aa08e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01999b17-51cf-44c4-8b74-4dc3e2d029ee" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_0c3cae9a-e5c6-4678-85df-7ed6c57aa08e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_5f46e92f-d245-454b-a103-622ce69a163e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_0c3cae9a-e5c6-4678-85df-7ed6c57aa08e" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_5f46e92f-d245-454b-a103-622ce69a163e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_26a886d1-a5eb-4c9e-97dc-cfac56ebc263" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_0c3cae9a-e5c6-4678-85df-7ed6c57aa08e" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_26a886d1-a5eb-4c9e-97dc-cfac56ebc263" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_9914419f-4493-4d45-bf48-3a4470381e68" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.blackdiamondtherapeutics.com/role/NETINCOMELOSSPERSHAREScheduleofComputationofNetIncomeLossperShareDetails" xlink:type="simple" xlink:href="bdtx-20260331.xsd#NETINCOMELOSSPERSHAREScheduleofComputationofNetIncomeLossperShareDetails"/>
  <link:definitionLink xlink:role="http://www.blackdiamondtherapeutics.com/role/NETINCOMELOSSPERSHAREScheduleofComputationofNetIncomeLossperShareDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareDilutedLineItems_019db5ec-04e6-7736-a586-84b6d6f2e39c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EarningsPerShareDilutedLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEarningsPerShareDilutedByCommonClassTable_019db5ec-04e6-7cda-a652-5817df7919f1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfEarningsPerShareDilutedByCommonClassTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EarningsPerShareDilutedLineItems_019db5ec-04e6-7736-a586-84b6d6f2e39c" xlink:to="loc_us-gaap_ScheduleOfEarningsPerShareDilutedByCommonClassTable_019db5ec-04e6-7cda-a652-5817df7919f1" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_019db5ec-04e6-7300-b45d-96de1e62bb7d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEarningsPerShareDilutedByCommonClassTable_019db5ec-04e6-7cda-a652-5817df7919f1" xlink:to="loc_us-gaap_AwardTypeAxis_019db5ec-04e6-7300-b45d-96de1e62bb7d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019db5ec-04e6-7300-b45d-96de1e62bb7d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_019db5ec-04e6-7300-b45d-96de1e62bb7d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019db5ec-04e6-7300-b45d-96de1e62bb7d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019db5ec-04e6-7f1b-b4e9-bdd3f5239db8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_019db5ec-04e6-7300-b45d-96de1e62bb7d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019db5ec-04e6-7f1b-b4e9-bdd3f5239db8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_019db5ec-04e6-77e9-b153-dd80e717913a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019db5ec-04e6-7f1b-b4e9-bdd3f5239db8" xlink:to="loc_us-gaap_EmployeeStockOptionMember_019db5ec-04e6-77e9-b153-dd80e717913a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_019db5ec-04e6-7b67-85ea-e729a644c2b8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019db5ec-04e6-7f1b-b4e9-bdd3f5239db8" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_019db5ec-04e6-7b67-85ea-e729a644c2b8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockMember_019db5ec-04e6-72b9-a629-dcd2ada5d26f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019db5ec-04e6-7f1b-b4e9-bdd3f5239db8" xlink:to="loc_us-gaap_EmployeeStockMember_019db5ec-04e6-72b9-a629-dcd2ada5d26f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_2193a578-6728-4215-ba26-c6ec7df15421" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareDilutedLineItems_019db5ec-04e6-7736-a586-84b6d6f2e39c" xlink:to="loc_us-gaap_NetIncomeLoss_2193a578-6728-4215-ba26-c6ec7df15421" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_76383977-da4f-4131-a471-91075f2297a0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareDilutedLineItems_019db5ec-04e6-7736-a586-84b6d6f2e39c" xlink:to="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_76383977-da4f-4131-a471-91075f2297a0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract_033a4d0f-03d6-414e-9f11-9735d6528c3e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareDilutedLineItems_019db5ec-04e6-7736-a586-84b6d6f2e39c" xlink:to="loc_us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract_033a4d0f-03d6-414e-9f11-9735d6528c3e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements_8d42c50d-8799-4b95-bb2c-de89a22cc8ad" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract_033a4d0f-03d6-414e-9f11-9735d6528c3e" xlink:to="loc_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements_8d42c50d-8799-4b95-bb2c-de89a22cc8ad" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_a6ebcde6-198f-4e1a-9b25-2db8ed262690" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareDilutedLineItems_019db5ec-04e6-7736-a586-84b6d6f2e39c" xlink:to="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_a6ebcde6-198f-4e1a-9b25-2db8ed262690" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareBasic_9351fab8-d054-47eb-9b41-4c7b301cf8d3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EarningsPerShareBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareDilutedLineItems_019db5ec-04e6-7736-a586-84b6d6f2e39c" xlink:to="loc_us-gaap_EarningsPerShareBasic_9351fab8-d054-47eb-9b41-4c7b301cf8d3" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareDiluted_18bda9ed-55bc-48c4-8ada-926961957946" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EarningsPerShareDiluted"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareDilutedLineItems_019db5ec-04e6-7736-a586-84b6d6f2e39c" xlink:to="loc_us-gaap_EarningsPerShareDiluted_18bda9ed-55bc-48c4-8ada-926961957946" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.blackdiamondtherapeutics.com/role/NETINCOMELOSSPERSHAREScheduleofAntidilutiveSecuritiesExcludedfromComputationofNetLossperShareDetails" xlink:type="simple" xlink:href="bdtx-20260331.xsd#NETINCOMELOSSPERSHAREScheduleofAntidilutiveSecuritiesExcludedfromComputationofNetLossperShareDetails"/>
  <link:definitionLink xlink:role="http://www.blackdiamondtherapeutics.com/role/NETINCOMELOSSPERSHAREScheduleofAntidilutiveSecuritiesExcludedfromComputationofNetLossperShareDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_45cf08d2-7939-4768-ad2c-aa30f6f9d83d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_898d2fac-d91a-49ee-9e69-5ca780858b34" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_45cf08d2-7939-4768-ad2c-aa30f6f9d83d" xlink:to="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_898d2fac-d91a-49ee-9e69-5ca780858b34" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_04322867-2eb5-4e5e-a778-3573121eea2c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_898d2fac-d91a-49ee-9e69-5ca780858b34" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_04322867-2eb5-4e5e-a778-3573121eea2c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_04322867-2eb5-4e5e-a778-3573121eea2c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_04322867-2eb5-4e5e-a778-3573121eea2c" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_04322867-2eb5-4e5e-a778-3573121eea2c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_d902e9bf-cd98-4894-a038-8706b1ddaa9f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_04322867-2eb5-4e5e-a778-3573121eea2c" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_d902e9bf-cd98-4894-a038-8706b1ddaa9f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_75452e44-c523-46f7-9ac1-995b96da9b5a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_d902e9bf-cd98-4894-a038-8706b1ddaa9f" xlink:to="loc_us-gaap_EmployeeStockOptionMember_75452e44-c523-46f7-9ac1-995b96da9b5a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockMember_019db5ed-6eaf-700f-8f8f-13b7f677e918" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RestrictedStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_d902e9bf-cd98-4894-a038-8706b1ddaa9f" xlink:to="loc_us-gaap_RestrictedStockMember_019db5ed-6eaf-700f-8f8f-13b7f677e918" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockMember_019db5ed-ba9a-7437-8153-4abd42751335" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_d902e9bf-cd98-4894-a038-8706b1ddaa9f" xlink:to="loc_us-gaap_EmployeeStockMember_019db5ed-ba9a-7437-8153-4abd42751335" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WarrantMember_c82ba8a0-3239-4e84-889c-0b2341e4f2ed" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_WarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_d902e9bf-cd98-4894-a038-8706b1ddaa9f" xlink:to="loc_us-gaap_WarrantMember_c82ba8a0-3239-4e84-889c-0b2341e4f2ed" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_02981b4f-6c41-4e4f-8e59-9fe0b77dec10" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_45cf08d2-7939-4768-ad2c-aa30f6f9d83d" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_02981b4f-6c41-4e4f-8e59-9fe0b77dec10" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.blackdiamondtherapeutics.com/role/LEASESNarrativeDetails" xlink:type="simple" xlink:href="bdtx-20260331.xsd#LEASESNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.blackdiamondtherapeutics.com/role/LEASESNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeLeaseDescriptionLineItems_65f27d3b-c437-42fd-9c07-291b4dd7db60" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LesseeLeaseDescriptionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeLeaseDescriptionTable_90198fce-a31a-49df-ac43-8da21b8cedfe" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LesseeLeaseDescriptionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_65f27d3b-c437-42fd-9c07-291b4dd7db60" xlink:to="loc_us-gaap_LesseeLeaseDescriptionTable_90198fce-a31a-49df-ac43-8da21b8cedfe" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LeaseContractualTermAxis_2d1fa85a-0e63-432f-928a-eaf15b5412f3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LeaseContractualTermAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LesseeLeaseDescriptionTable_90198fce-a31a-49df-ac43-8da21b8cedfe" xlink:to="loc_us-gaap_LeaseContractualTermAxis_2d1fa85a-0e63-432f-928a-eaf15b5412f3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LeaseContractualTermDomain_2d1fa85a-0e63-432f-928a-eaf15b5412f3_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LeaseContractualTermDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LeaseContractualTermAxis_2d1fa85a-0e63-432f-928a-eaf15b5412f3" xlink:to="loc_us-gaap_LeaseContractualTermDomain_2d1fa85a-0e63-432f-928a-eaf15b5412f3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LeaseContractualTermDomain_2ae1f9cd-6559-420b-9a5f-311378158b2a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LeaseContractualTermDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LeaseContractualTermAxis_2d1fa85a-0e63-432f-928a-eaf15b5412f3" xlink:to="loc_us-gaap_LeaseContractualTermDomain_2ae1f9cd-6559-420b-9a5f-311378158b2a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_OperatingLeasePrincipalOfficeJuly2020LeaseMember_019d3d56-c5fe-757b-b574-445e1aeeccbf" xlink:href="bdtx-20260331.xsd#bdtx_OperatingLeasePrincipalOfficeJuly2020LeaseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LeaseContractualTermDomain_2ae1f9cd-6559-420b-9a5f-311378158b2a" xlink:to="loc_bdtx_OperatingLeasePrincipalOfficeJuly2020LeaseMember_019d3d56-c5fe-757b-b574-445e1aeeccbf" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_OperatingLeaseOfficeAndLaboratorySpaceNYMember_c7153143-e60f-4624-ae67-4389e683df43" xlink:href="bdtx-20260331.xsd#bdtx_OperatingLeaseOfficeAndLaboratorySpaceNYMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LeaseContractualTermDomain_2ae1f9cd-6559-420b-9a5f-311378158b2a" xlink:to="loc_bdtx_OperatingLeaseOfficeAndLaboratorySpaceNYMember_c7153143-e60f-4624-ae67-4389e683df43" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_LesseeOperatingLeaseNumberOfContracts_78dc715e-0a0d-40c1-91a1-52a26ed4c762" xlink:href="bdtx-20260331.xsd#bdtx_LesseeOperatingLeaseNumberOfContracts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_65f27d3b-c437-42fd-9c07-291b4dd7db60" xlink:to="loc_bdtx_LesseeOperatingLeaseNumberOfContracts_78dc715e-0a0d-40c1-91a1-52a26ed4c762" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseImpairmentLoss_019d3d58-c26a-7950-9e24-05885b15b6f0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OperatingLeaseImpairmentLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_65f27d3b-c437-42fd-9c07-291b4dd7db60" xlink:to="loc_us-gaap_OperatingLeaseImpairmentLoss_019d3d58-c26a-7950-9e24-05885b15b6f0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ImpairmentOfLongLivedAssetsHeldForUse_019d3d58-c26a-7ac7-9103-362dd28672aa" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ImpairmentOfLongLivedAssetsHeldForUse"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_65f27d3b-c437-42fd-9c07-291b4dd7db60" xlink:to="loc_us-gaap_ImpairmentOfLongLivedAssetsHeldForUse_019d3d58-c26a-7ac7-9103-362dd28672aa" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.blackdiamondtherapeutics.com/role/SEGMENTREPORTINGScheduleofCompanysReportableSegmentDetails" xlink:type="simple" xlink:href="bdtx-20260331.xsd#SEGMENTREPORTINGScheduleofCompanysReportableSegmentDetails"/>
  <link:definitionLink xlink:role="http://www.blackdiamondtherapeutics.com/role/SEGMENTREPORTINGScheduleofCompanysReportableSegmentDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingInformationLineItems_da6a4447-f1bf-4fdc-9005-01ba6b39ce83" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SegmentReportingInformationLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_67b3eed3-15dc-49cf-8661-98eb5f16adac" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_da6a4447-f1bf-4fdc-9005-01ba6b39ce83" xlink:to="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_67b3eed3-15dc-49cf-8661-98eb5f16adac" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementBusinessSegmentsAxis_a64841f7-6c29-4404-8cdd-d5c6d37afe52" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementBusinessSegmentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_67b3eed3-15dc-49cf-8661-98eb5f16adac" xlink:to="loc_us-gaap_StatementBusinessSegmentsAxis_a64841f7-6c29-4404-8cdd-d5c6d37afe52" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_a64841f7-6c29-4404-8cdd-d5c6d37afe52_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_a64841f7-6c29-4404-8cdd-d5c6d37afe52" xlink:to="loc_us-gaap_SegmentDomain_a64841f7-6c29-4404-8cdd-d5c6d37afe52_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_a48a93c1-7cbd-4986-b79c-e6e664a8504f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_a64841f7-6c29-4404-8cdd-d5c6d37afe52" xlink:to="loc_us-gaap_SegmentDomain_a48a93c1-7cbd-4986-b79c-e6e664a8504f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_ReportableSegmentMember_ef013e95-a797-415a-9fee-0ce39e08d817" xlink:href="bdtx-20260331.xsd#bdtx_ReportableSegmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentDomain_a48a93c1-7cbd-4986-b79c-e6e664a8504f" xlink:to="loc_bdtx_ReportableSegmentMember_ef013e95-a797-415a-9fee-0ce39e08d817" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_1faf2f09-2edd-4764-87b0-fd2e5733f3ad" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_67b3eed3-15dc-49cf-8661-98eb5f16adac" xlink:to="loc_srt_ProductOrServiceAxis_1faf2f09-2edd-4764-87b0-fd2e5733f3ad" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_1faf2f09-2edd-4764-87b0-fd2e5733f3ad_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_1faf2f09-2edd-4764-87b0-fd2e5733f3ad" xlink:to="loc_srt_ProductsAndServicesDomain_1faf2f09-2edd-4764-87b0-fd2e5733f3ad_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_3d48480e-3a74-48f2-b399-f090cc038810" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_1faf2f09-2edd-4764-87b0-fd2e5733f3ad" xlink:to="loc_srt_ProductsAndServicesDomain_3d48480e-3a74-48f2-b399-f090cc038810" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_ResearchAndDevelopmentSilevertinibNSCLCMember_019db5ef-453d-7e71-9103-6aa8fa7bced8" xlink:href="bdtx-20260331.xsd#bdtx_ResearchAndDevelopmentSilevertinibNSCLCMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_3d48480e-3a74-48f2-b399-f090cc038810" xlink:to="loc_bdtx_ResearchAndDevelopmentSilevertinibNSCLCMember_019db5ef-453d-7e71-9103-6aa8fa7bced8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_ResearchAndDevelopmentSilevertinibGBMMember_019db5ef-453d-70a9-a15d-5ce2f43f60f0" xlink:href="bdtx-20260331.xsd#bdtx_ResearchAndDevelopmentSilevertinibGBMMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_3d48480e-3a74-48f2-b399-f090cc038810" xlink:to="loc_bdtx_ResearchAndDevelopmentSilevertinibGBMMember_019db5ef-453d-70a9-a15d-5ce2f43f60f0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_ResearchAndDevelopmentBDTX4933Member_4dce97e8-8961-44b2-b125-0624d0175ff5" xlink:href="bdtx-20260331.xsd#bdtx_ResearchAndDevelopmentBDTX4933Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_3d48480e-3a74-48f2-b399-f090cc038810" xlink:to="loc_bdtx_ResearchAndDevelopmentBDTX4933Member_4dce97e8-8961-44b2-b125-0624d0175ff5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_ResearchAndDevelopmentOtherMember_1937acd5-300e-41a2-8986-7bca60641a75" xlink:href="bdtx-20260331.xsd#bdtx_ResearchAndDevelopmentOtherMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_3d48480e-3a74-48f2-b399-f090cc038810" xlink:to="loc_bdtx_ResearchAndDevelopmentOtherMember_1937acd5-300e-41a2-8986-7bca60641a75" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_45e48b78-0734-476f-ab7b-b42d1c70d3e8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_da6a4447-f1bf-4fdc-9005-01ba6b39ce83" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_45e48b78-0734-476f-ab7b-b42d1c70d3e8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_da6677c9-6c4f-4996-8ad8-5fcec8dc8b63" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_da6a4447-f1bf-4fdc-9005-01ba6b39ce83" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_da6677c9-6c4f-4996-8ad8-5fcec8dc8b63" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_NonProgramExpense_4fca46a5-2d91-4e95-a25b-843de5ea251c" xlink:href="bdtx-20260331.xsd#bdtx_NonProgramExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_da6a4447-f1bf-4fdc-9005-01ba6b39ce83" xlink:to="loc_bdtx_NonProgramExpense_4fca46a5-2d91-4e95-a25b-843de5ea251c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LaborAndRelatedExpense_6b6140fb-a999-483f-a735-ad5e7519c101" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LaborAndRelatedExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_da6a4447-f1bf-4fdc-9005-01ba6b39ce83" xlink:to="loc_us-gaap_LaborAndRelatedExpense_6b6140fb-a999-483f-a735-ad5e7519c101" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingOtherItemAmount_f16d63bf-c14e-4c89-9094-511a063a568c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SegmentReportingOtherItemAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_da6a4447-f1bf-4fdc-9005-01ba6b39ce83" xlink:to="loc_us-gaap_SegmentReportingOtherItemAmount_f16d63bf-c14e-4c89-9094-511a063a568c" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_b2ea4d4a-ecf6-41f9-b2ac-44c3e4c4531e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_da6a4447-f1bf-4fdc-9005-01ba6b39ce83" xlink:to="loc_us-gaap_NetIncomeLoss_b2ea4d4a-ecf6-41f9-b2ac-44c3e4c4531e" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.blackdiamondtherapeutics.com/role/LICENSEREVENUEDetails" xlink:type="simple" xlink:href="bdtx-20260331.xsd#LICENSEREVENUEDetails"/>
  <link:definitionLink xlink:role="http://www.blackdiamondtherapeutics.com/role/LICENSEREVENUEDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueLineItems_6d5e482b-604f-4a45-8cee-d7a565f2351b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DisaggregationOfRevenueLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueTable_cf031875-2289-4287-8109-b2931a3a4978" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DisaggregationOfRevenueTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_6d5e482b-604f-4a45-8cee-d7a565f2351b" xlink:to="loc_us-gaap_DisaggregationOfRevenueTable_cf031875-2289-4287-8109-b2931a3a4978" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_1b52ee03-985d-4ffd-aadf-9eeb13cfeffc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_cf031875-2289-4287-8109-b2931a3a4978" xlink:to="loc_us-gaap_TypeOfArrangementAxis_1b52ee03-985d-4ffd-aadf-9eeb13cfeffc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_1b52ee03-985d-4ffd-aadf-9eeb13cfeffc_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_1b52ee03-985d-4ffd-aadf-9eeb13cfeffc" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_1b52ee03-985d-4ffd-aadf-9eeb13cfeffc_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_945dc2f7-019d-4f90-9766-de5d509241b0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_1b52ee03-985d-4ffd-aadf-9eeb13cfeffc" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_945dc2f7-019d-4f90-9766-de5d509241b0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_ServierAgreementMember_8167684f-37b8-4350-9191-72657075642c" xlink:href="bdtx-20260331.xsd#bdtx_ServierAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_945dc2f7-019d-4f90-9766-de5d509241b0" xlink:to="loc_bdtx_ServierAgreementMember_8167684f-37b8-4350-9191-72657075642c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_CollaborativeArrangementUpfrontPayment_9800a8df-cbf7-49f5-9a9e-7739db07e9f8" xlink:href="bdtx-20260331.xsd#bdtx_CollaborativeArrangementUpfrontPayment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_6d5e482b-604f-4a45-8cee-d7a565f2351b" xlink:to="loc_bdtx_CollaborativeArrangementUpfrontPayment_9800a8df-cbf7-49f5-9a9e-7739db07e9f8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_CollaborativeArrangementMilestonePayments_9cda1312-ec40-4d94-9ecb-bcda8e2fc507" xlink:href="bdtx-20260331.xsd#bdtx_CollaborativeArrangementMilestonePayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_6d5e482b-604f-4a45-8cee-d7a565f2351b" xlink:to="loc_bdtx_CollaborativeArrangementMilestonePayments_9cda1312-ec40-4d94-9ecb-bcda8e2fc507" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_627f7a30-f0a2-47fa-a415-73d13e7d9b20" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_6d5e482b-604f-4a45-8cee-d7a565f2351b" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_627f7a30-f0a2-47fa-a415-73d13e7d9b20" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://fasb.org/us-gaap/role/eedm/ExtensibleEnumerationLists" xlink:type="simple" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-roles-2025.xsd#eedm"/>
  <link:definitionLink xlink:role="http://fasb.org/us-gaap/role/eedm/ExtensibleEnumerationLists" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrentAbstract" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LiabilitiesCurrentAbstract"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedLiabilitiesCurrent" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccruedLiabilitiesCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesCurrentAbstract" xlink:to="loc_us-gaap_AccruedLiabilitiesCurrent" xlink:type="arc" order="41"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://xbrl.sec.gov/ecd/role/IndividualsOnly" xlink:type="simple" xlink:href="https://xbrl.sec.gov/ecd/2025/ecd-2025.xsd#IndividualsOnly"/>
  <link:definitionLink xlink:role="http://xbrl.sec.gov/ecd/role/IndividualsOnly" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_ecd_AllIndividualsMember" xlink:href="https://xbrl.sec.gov/ecd/2025/ecd-2025.xsd#ecd_AllIndividualsMember"/>
    <link:loc xlink:type="locator" xlink:label="loc_bdtx_ElizabethBuckMember_b71a1ad8-69a5-4fa7-a6bf-da9c4a863175" xlink:href="bdtx-20260331.xsd#bdtx_ElizabethBuckMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_ecd_AllIndividualsMember" xlink:to="loc_bdtx_ElizabethBuckMember_b71a1ad8-69a5-4fa7-a6bf-da9c4a863175" xlink:type="arc" order="2"/>
  </link:definitionLink>
</link:linkbase>
