Objective: To investigate the diagnostic and therapeutic characteristics of synchronous quadruple primary malignancies.Methods: The clinical data of a 46-year-old man with synchronous quadruple primary malignancies were retrospectively analyzed, together with the findings of pathological examination, immunohistochemistry, and genetic testing.Results: The patient was diagnosed with papillary thyroid carcinoma of the left lobe, mucinous adenocarcinoma of the ileocecal region, and moderately to poorly differentiated adenocarcinomas of the transverse and ascending colon. Immunohistochemistry showed loss of MLH1/PMS2 protein expression in the colorectal cancer tissues, and genetic testing identified a pathogenic germline variant in MLH1, confirming Lynch syndrome. The patient underwent synchronous radical resection of the thyroid and colorectal tumors, followed by adjuvant oxaliplatin-based chemotherapy. No obvious evidence of recurrence or metastasis was observed during follow-up.Conclusion: Synchronous quadruple primary malignancies are rare. In patients presenting with multiple primary tumors and a relevant family history, pathological and molecular genetic testing should be considered to establish an accurate diagnosis and guide individualized treatment and cascade screening of at-risk family members.