Thyroglossal duct cyst is an unusual developmental cyst of the neck, arising anywhere from the base of the tongue to the thyroid gland. It may develop from epithelial remnants of the thyroglossal duct. To determine whether apoptotic cell death or cell proliferation has a role in the formation of this cyst, apoptosis-related factors and cell proliferation markers were immunohistochemically examined in the thyroglossal ducts and thyroglossal duct cysts. Expression of Lewis^y antigen was detected in the lining epithelium of all thyroglossal duct cysts and in the luminal epithelium of all thyroglossal ducts. Immunoreactivity for p53 protein was detected only in the lining epithelium with squamous metaplasia in thyroglossal duct cysts and was not detected in the thyroglossal ducts. Expression of bcl-2 protein was detected in several thyroglossal duct cysts as well as in the thyroglossal ducts, and the proportion of cases positive for bcl-2 protein was significantly higher in thyroglossal duct cysts than in the thyroglossal ducts (p<0.05). The ratio of Ki-67-positive cells (Ki-67-LI) in thyroglossal duct cysts was significantly higher than that in the thyroglossal ducts (p<0.05). These immunohistochemical features suggest that apoptosis-related factors and cell proliferation markers might play specific roles in cyst formation in the thyroglossal ducts.