Thyroglossal cysts are common developmental abnormalities of the thyroid gland. The malignant form of these cysts, however, is extremely rare, with fewer than 100 cases reported since 1915. Here we add 10 cases of malignant thyroglossal cysts, nine women and one man, encountered at M.D. Anderson Cancer Center, based on a retrospective review of 51 recorded cases of thyroglossal cysts between 1950 and 1990. All 10 patients underwent a primary Sistrunk procedure. Histologic findings showed nine papillary and one follicular carcinoma. Based on review of the histopathologic material, four patients required no additional therapy. Five patients underwent total thyroidectomy; three of the five also underwent neck dissection. A single microscopic focus of carcinoma in the thyroid gland was found in only two instances. No evidence of nodal metastases was found. One patient with an abnormal thyroid scan is awaiting further treatment. Based on these findings, the Sistrunk procedure is an effective form of therapy for malignant thyrogloassal cysts.