BACKGROUND: Medullary thyroid cancer, a tumor of the parafollicular C cells, accounts for approximately 10% of all thyroid malignancies. An estimated 75% of cases are sporadic, and the remaining 25% are familial. METHODS: The author reviews the clinical features and diagnostic tests for this entity, as well as the surgical treatment of recurrent or persistent medullary carcinoma. RESULTS: Sporadic medullary thyroid cancer typically presents as an isolated unilateral mass. Familial tumors tend to be multifocal and bilateral. In patients with multiple endocrine neoplasia type 2A, pheochromocytomas and parathyroid hyperplasia also may develop. Care is taken to avoid operating on a patient with occult pheochromocytoma. Total thyroidectomy and central lymph node dissection are the keys for successful surgical treatment. CONCLUSIONS: Surgery is the cornerstone of treatment for medullary carcinoma of the thyroid. Genetic testing using the ret oncogene allows identification of individuals who are at risk for the disease or those with early-stage disease.