Medullary thyroid carcinoma (MTC) is a malignant tumor originating from thyroid parafollicular C cells and accounts for only <5% of thyroid cancers, but it causes a disproportionate number of thyroid cancer deaths due to its more aggressive clinical behavior compared with well-differentiated papillary and follicular thyroid carcinomas. A subset of MTC cases is hereditary and due to germline mutations in the RET tyrosine kinase receptor gene. Somatic mutations in either RET or RAS are also present in most sporadic tumors. In MTC, RET mutations lead to substrate-independent dimerization of the receptor causing constitutive activation, unrestricted signaling, and ultimately, cancer.