<?xml version="1.0"?>
<ownershipDocument>

    <schemaVersion>X0206</schemaVersion>

    <documentType>3</documentType>

    <periodOfReport>2021-10-01</periodOfReport>

    <noSecuritiesOwned>1</noSecuritiesOwned>

    <issuer>
        <issuerCik>0000810509</issuerCik>
        <issuerName>NAVIDEA BIOPHARMACEUTICALS, INC.</issuerName>
        <issuerTradingSymbol>NAVB</issuerTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001886391</rptOwnerCik>
            <rptOwnerName>Mikhail Michel</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>4995 BRADENTON AVE., SUITE 240</rptOwnerStreet1>
            <rptOwnerStreet2></rptOwnerStreet2>
            <rptOwnerCity>DUBLIN</rptOwnerCity>
            <rptOwnerState>OH</rptOwnerState>
            <rptOwnerZipCode>43017</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isOfficer>1</isOfficer>
            <officerTitle>Chief Regulatory Officer</officerTitle>
        </reportingOwnerRelationship>
    </reportingOwner>

    <ownerSignature>
        <signatureName>/s/ Jed A. Latkin for Michel Mikhail, by Power of Attorney</signatureName>
        <signatureDate>2021-10-05</signatureDate>
    </ownerSignature>
</ownershipDocument>
