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Introduction: Medullary thyroid carcinoma (MTC) comprises nearly 5% of all cases of thyroid cancer (TC). Aberrant activation of RET (rearranged during transfection) signaling via somatic mutations is the basic molecular mechanism of MTC tumorigenicity. In this study, we determined the incidence of RET gene mutations in exons 10, 11, and 16 in Iranian patients. Methods: A total of 33 patients undergoing thyroidectomy at Imam Khomeini hospital of Tehran, Iran and diagnosed with MTC were enrolled. For investigating mutations in exons 10, 11, and 16, DNA was extracted from tumor tissues, and the genes were amplified by polymerase chain reaction (PCR) and then sequenced. Results: Out of 33 patients, 20 (60.6%) subjects had mutations in one of the examined exons (10, 11, and 16). According to our results, the "ATG918ACG" mutation in codon 918 had the highest rate. Conclusion: Testing RET mutations can be beneficial in clinical evaluation and treatment management of MTC patients.