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Familial non-medullary, follicular cell-derived thyroid neoplasms represent a genetically diverse and under-recognized group of tumors arising from follicular epithelial cells. These familial thyroid tumors are subclassified into syndromes where thyroid tumors represent the major disease manifestation and syndromes with a predominance of non-thyroid neoplasms. Among the latter group, germline mutations in the DICER1 and PTEN genes are increasingly implicated in syndromic forms of follicular-derived thyroid disease. DICER1 syndrome and PTEN-hamartoma tumor syndrome, encompassing Cowden syndrome and related entities, confer a high organ-specific predisposition to benign and malignant thyroid lesions. Both syndromes demonstrate distinctive clinicopathologic patterns, including early-onset thyroid follicular nodular disease, multifocal follicular adenomas, and increased risk for thyroid malignancies. Recognizing clinical, anatomical, and histomorphological clues when evaluating thyroid specimens (particularly bilateral nodules, multinodularity, histologically distinct neoplasms, multiple adenomatous nodules, macrofollicular pattern, oncocytic features, unusual adenoma subtypes, young male gender, or early presentation) can prompt genetic evaluation. Here, we review the molecular pathogenesis, clinical features, histologic spectrum, and diagnostic strategies associated with familial follicular cell-derived thyroid tumors caused by DICER1 and PTEN germline alterations. Increased awareness of these entities by pathologists and clinicians is critical to ensure timely diagnosis, risk-appropriate surveillance, and cascade testing in affected families.