Medullary thyroid carcinoma (MTC) accounts for 5-8% of all thyroid cancers. MTC is mainly sporadic in nature, but an hereditary pattern [multiple endocrine neoplasia type 2 (MEN 2)] is present in 20-30% of cases, transmitted as an autosomal-dominant trait due to germline mutations of the RET proto-oncogene. About 98% of patients with MEN 2 have germline mutations in exons 5, 8, 10, 11, 13, 14, 15 or 16 of the RET gene. The primary treatment of both hereditary and sporadic forms of MTC is total thyroidectomy and removal of all neoplastic tissue present in the neck. The therapeutic option for lymph node surgery should be dictated by the results of presurgical evaluation. After total thyroidectomy, measurements of serum calcitonin (CT) and carcinoembryonic antigen are of paramount importance in the postsurgical follow-up of patients with MTC as they reflect the presence of persistent or recurrent disease. Complete remission is demonstrated by undetectable and stimulated serum CT measurement. On the contrary, if serum CT is detectable under basal conditions or becomes detectable after stimulation, the patient is probably not cured, but imaging techniques will not demonstrate any disease until serum CT approaches levels >150 pg/ml. The tumour metastasises early to both paratracheal and lateral cervical lymph nodes. Metastases outside the neck may occur in the liver, lungs, bones and, less frequently, brain and skin. Surgery is the main treatment for local and distant metastases whenever feasible. Systemic chemotherapy with dacarbazine, 5-fluorouracil and doxorubicin (alone or in combination) has shown very limited efficacy, achieving only partial responses in the range of 10-20% and of short duration. Several kinase inhibitors are currently under evaluation and preliminary results are promising. Familial cases must be identified by searching for RET proto-oncogene mutations in the proband and in family members. Carriers of the RET gene are candidates for prophylactic thyroidectomy at different ages depending on the risk associated with the specific RET mutations.