Thyroid cancer is rare in childhood and consists of several different histopathologic groups with widely varying clinical behavior. Major categories include differentiated, medullary, and anaplastic thyroid cancer. Non-Hodgkin's lymphoma and various sarcomas also can arise in the thyroid. This article discusses differentiated and medullary thyroid cancer in childhood and adolescence. Differentiated thyroid carcinoma is divided into three subtypes: papillary, papillary with follicular elements, and follicular. Medullary tumors may occur in isolation but more frequently are associated with one of the multiple endocrine neoplasia syndromes (MEN). A paradoxical observation concerning patients with differentiated thyroid cancer is that 70% to 80% present with regional lymph node involvement, and more than 20% have distant metastases at diagnosis. However, survival rates in series with median follow-ups of 10 to 20 years have been 90% to 100%. These data have implications for the surgical management of pediatric patients with differentiated thyroid cancer. The cellular and genetic factors that underlie this paradoxical behavior are not understood. Management of children with medullary thyroid cancer was revolutionized by the identification of specific mutations in the ret oncogene that predict for multiple endocrine neoplasia syndromes. This has allowed sensitive and specific diagnosis based on analysis of the patient's white blood cells. Because this leads to earlier diagnosis, total thyroidectomy can be performed at a much earlier age than if the increase in serum calcitonin was used to identify C-cell hyperplasia or early carcinoma. At present, genetic testing should be performed at birth in children suspected of having the MEN IIb syndrome and no later than 1 year of age for those with possible MEN IIa. If specific ret gene mutations are noted, total thyroidectomy is recommended as soon as the diagnosis is established. For MEN IIa patients, thyroidectomy probably should be performed before 5 years of age, whereas patients with MEN IIb may require surgery during the first 6 months to 1 year of life.