Medullary thyroid carcinoma, comprising approximately 7% of thyroid carcinoma, produces calcitonin, which can be monitored by immunoassay for diagnosis, at preclinical stages, and for persistent disease and its extent. It presents as sporadic and hereditary forms. The latter consists of the multiple endocrine neoplasia (MEN)-2A syndrome, which includes pheochromocytomas and hyperparathyroidism in some families, and the MEN-2B syndrome, which consistently includes mucosal neuromas and somatic features. The carcinoma, especially the MEN-2B variety, is more aggressive than well-differentiated thyroid carcinoma. After the presence and management of a possible pheochromocytoma is resolved, treatment is by total thyroidectomy, the MEN-2 syndromes always indicating bilateral involvement. Gross evidence of medullary thyroid carcinoma is associated with metastases to regional lymph nodes, justifying removal of lymph nodes in the central neck, anterior superior mediastinum, and lateral neck. At operation, attention is given to preservation of parathyroid glands but also to removal of hyperplastic parathyroid glands; subtotal parathyroidectomy usually is needed if clinical hyperparathyroidism is evident. Diagnosis at the preclinical stage, C-cell hyperplasia, permits total thyroidectomy. Lateral cervical lymph node dissection is determined by biopsy of midjugular lymph nodes. In this situation, serum calcitonin levels are usually normal after operation, indicating cure. However, for palpable medullary thyroid carcinoma, serum calcitonin levels are often elevated after appropriate neck surgery. In this event, scanning techniques are used to monitor patients, and reoperation is performed if localization of medullary thyroid carcinoma is achieved. The mediastinum is particularly observed for recurrence. Reoperation is justified for recurrence in the neck and mediastinum. Early diagnosis and monitoring permits long-term survival. In the future it is anticipated that diagnostic genetic techniques will provide definitive and early diagnosis in the hereditary form, permitting earlier treatment with assurance of cure.