Mutations in the *DICER1* gene, which is involved in RNA interference, have been linked to a wide range of multi-organ neoplastic and non-neoplastic conditions. Historically associated with pleuropulmonary blastoma, DICER1 syndrome has gained more attention due to its association with newly discovered diseases and tumors. Recent studies have revealed that thyroid disease is the most common manifestation of *DICER1* mutations, particularly thyroid follicular nodular disease (TFND) and differentiated thyroid carcinomas in infants. These conditions are highly specific indicators of germline *DICER1* mutations or DICER1 syndrome. Additionally, poorly differentiated thyroid carcinomas and thyroblastomas are potential indicators of somatic *DICER1* mutations. Recognizing these manifestations should prompt clinicians to expedite genetic evaluation for this neoplastic syndrome and classify patients as high-risk for additional multi-organ malignancies. This study provides a comprehensive investigation into *DICER1* mutations, focusing on their role in thyroid diseases, and highlights the importance of histologic findings for diagnosis.Mutations in the *DICER1* gene, which is involved in RNA interference, have been linked to a wide range of multi-organ neoplastic and non-neoplastic conditions. Historically associated with pleuropulmonary blastoma, DICER1 syndrome has gained more attention due to its association with newly discovered diseases and tumors. Recent studies have revealed that thyroid disease is the most common manifestation of *DICER1* mutations, particularly thyroid follicular nodular disease (TFND) and differentiated thyroid carcinomas in infants. These conditions are highly specific indicators of germline *DICER1* mutations or DICER1 syndrome. Additionally, poorly differentiated thyroid carcinomas and thyroblastomas are potential indicators of somatic *DICER1* mutations. Recognizing these manifestations should prompt clinicians to expedite genetic evaluation for this neoplastic syndrome and classify patients as high-risk for additional multi-organ malignancies. This study provides a comprehensive investigation into *DICER1* mutations, focusing on their role in thyroid diseases, and highlights the importance of histologic findings for diagnosis.