<?xml version="1.0" encoding="UTF-8"?><edgarSubmission xmlns="http://www.sec.gov/edgar/ownership" xmlns:com="http://www.sec.gov/edgar/common">
  <!-- Generated by Workiva -->
  <headerData>
    <submissionType>144</submissionType>
    <filerInfo>
      <filer>
        <filerCredentials>
          <cik>0001856565</cik>
          <ccc>XXXXXXXX</ccc>
        </filerCredentials>
      </filer>
      <liveTestFlag>LIVE</liveTestFlag>



    </filerInfo>
  </headerData>
  <formData>
    <issuerInfo>
      <issuerCik>0001447362</issuerCik>
      <issuerName>Castle Biosciences, Inc.</issuerName>
      <secFileNumber>001-38984</secFileNumber>
      <issuerAddress>
        <com:street1>505 S. Friendswood Drive, Suite 401</com:street1>
        <com:city>Friendswood</com:city>
        <com:stateOrCountry>TX</com:stateOrCountry>
        <com:zipCode>77546</com:zipCode>
      </issuerAddress>
      <issuerContactPhone>866-788-9007</issuerContactPhone>
      <nameOfPersonForWhoseAccountTheSecuritiesAreToBeSold>Kristen M. Oelschlager</nameOfPersonForWhoseAccountTheSecuritiesAreToBeSold>
      <relationshipsToIssuer>
        <relationshipToIssuer>Officer</relationshipToIssuer>
      </relationshipsToIssuer>
    </issuerInfo>
    <securitiesInformation>
      <securitiesClassTitle>Common Stock</securitiesClassTitle>
      <brokerOrMarketmakerDetails>
        <name>J.P. Morgan Securities LLC</name>
        <address>
          <com:street1>270 Park Avenue, 10th Floor</com:street1>
          <com:city>New York</com:city>
          <com:stateOrCountry>NY</com:stateOrCountry>
          <com:zipCode>10017</com:zipCode>
        </address>
      </brokerOrMarketmakerDetails>
      <noOfUnitsSold>18932</noOfUnitsSold>
      <aggregateMarketValue>657698</aggregateMarketValue>
      <noOfUnitsOutstanding>29188659</noOfUnitsOutstanding>
      <approxSaleDate>11/11/2025</approxSaleDate>
      <securitiesExchangeName>NASDAQ</securitiesExchangeName>
    </securitiesInformation>
    <securitiesToBeSold>
      <securitiesClassTitle>Common Stock</securitiesClassTitle>
      <acquiredDate>12/29/2023</acquiredDate>
      <natureOfAcquisitionTransaction>ISO</natureOfAcquisitionTransaction>
      <nameOfPersonfromWhomAcquired>Issuer</nameOfPersonfromWhomAcquired>
      <isGiftTransaction>N</isGiftTransaction>
      <amountOfSecuritiesAcquired>8000</amountOfSecuritiesAcquired>
      <paymentDate>12/29/2023</paymentDate>
      <natureOfPayment>Cash</natureOfPayment>
    </securitiesToBeSold>
    <securitiesToBeSold>
      <securitiesClassTitle>Common Stock</securitiesClassTitle>
      <acquiredDate>04/05/2019</acquiredDate>
      <natureOfAcquisitionTransaction>Founder Shares</natureOfAcquisitionTransaction>
      <nameOfPersonfromWhomAcquired>Issuer</nameOfPersonfromWhomAcquired>
      <isGiftTransaction>N</isGiftTransaction>
      <amountOfSecuritiesAcquired>10932</amountOfSecuritiesAcquired>
      <paymentDate>04/05/2019</paymentDate>
      <natureOfPayment>Cash</natureOfPayment>
    </securitiesToBeSold>
    <nothingToReportFlagOnSecuritiesSoldInPast3Months>N</nothingToReportFlagOnSecuritiesSoldInPast3Months>
    <securitiesSoldInPast3Months>
      <sellerDetails>
        <name>Kristen M. Oelschlager</name>
        <address>
          <com:street1>C/o Castle Biosciences, Inc.</com:street1>
          <com:street2>505 S. Friendswood Drive, Suite 401</com:street2>
          <com:city>Friendswood</com:city>
          <com:stateOrCountry>TX</com:stateOrCountry>
          <com:zipCode>77546</com:zipCode>
        </address>
      </sellerDetails>
      <securitiesClassTitle>Common Stock</securitiesClassTitle>
      <saleDate>08/27/2025</saleDate>
      <amountOfSecuritiesSold>12677</amountOfSecuritiesSold>
      <grossProceeds>279140</grossProceeds>
    </securitiesSoldInPast3Months>
    <securitiesSoldInPast3Months>
      <sellerDetails>
        <name>Kristen M. Oelschlager</name>
        <address>
          <com:street1>C/o Castle Biosciences, Inc.</com:street1>
          <com:street2>505 S. Friendswood Drive, Suite 401</com:street2>
          <com:city>Friendswood</com:city>
          <com:stateOrCountry>TX</com:stateOrCountry>
          <com:zipCode>77546</com:zipCode>
        </address>
      </sellerDetails>
      <securitiesClassTitle>Common Stock</securitiesClassTitle>
      <saleDate>10/31/2025</saleDate>
      <amountOfSecuritiesSold>12678</amountOfSecuritiesSold>
      <grossProceeds>317503</grossProceeds>
    </securitiesSoldInPast3Months>
    <securitiesSoldInPast3Months>
      <sellerDetails>
        <name>The Fritz Shorter Trust</name>
        <address>
          <com:street1>C/o Castle Biosciences, Inc.</com:street1>
          <com:street2>505 S. Friendswood Drive, Suite 401</com:street2>
          <com:city>Friendswood</com:city>
          <com:stateOrCountry>TX</com:stateOrCountry>
          <com:zipCode>77546</com:zipCode>
        </address>
      </sellerDetails>
      <securitiesClassTitle>Common Stock</securitiesClassTitle>
      <saleDate>08/27/2025</saleDate>
      <amountOfSecuritiesSold>18007</amountOfSecuritiesSold>
      <grossProceeds>390595</grossProceeds>
    </securitiesSoldInPast3Months>
    <remarks>Sales that were executed on 11/11/25 are being reported on this Form 144 filed on 11/12/25  given the EDGAR system was not accepting filings on 11/11/25 in observance of the federal holiday.</remarks>
    <noticeSignature>
      <noticeDate>11/12/2025</noticeDate>
      <planAdoptionDates>
        <planAdoptionDate>03/06/2025</planAdoptionDate>
      </planAdoptionDates>
      <signature>/s/ J.P. Morgan Securities LLC as agent and attorney-in-fact for Kristen M. Oelschlager.</signature>
    </noticeSignature>
  </formData>
</edgarSubmission>
