Medullary thyroid cancer (MTC) is a distinct C-cell tumor of the thyroid. We review the oncogenesis and management of both sporadic tumors and those tumors arising as part of specific inherited syndromes. The RET proto-oncogene plays a role in the development of inherited forms of MTC and has become important in the clinical management of patients and their families. The recognition of the high rate of regional nodal involvement has led to lymphadenectomy being strongly considered for patients undergoing thyroidectomy for MTC.