BACKGROUND Because medullary thyroid carcinoma accounts for only 7% of all thyroid malignancies, data to support treatment strategies are scarce. METHODS We retrospectively reviewed treatment and outcome in 34 patients with MTC treated at Roswell Park between 1961 and 1995. Univariate analysis was performed using the variables age, sex, tumor size, N stage, and M stage. RESULTS Median survival was 4.7 years, with 51% and 32% of patients alive at 5 and 15 years, respectively. Nodal metastases were seen in 76% and distant metastases in 67% of all patients. More than 60% of the patients with nodal metastases survived longer than 10 years. Once diagnosed with distant metastases, 90% of the patients died within 5 years. Local failure rate with lobectomy was 44%, compared to 10% after total thyroidectomy (P < .02). Age, extrathyroid extension, and M stage portend a poor outcome. Nodal status had no statistically significant impact on survival. CONCLUSIONS Survival with tumors confined to the thyroid gland is independent of nodal status. Long-term survival in patients with distant metastases is rare. This study underscores the role of total thyroidectomy in the initial treatment and the need to develop effective adjuvant therapy for MTC.