The clinical and diagnostic findings of 3 cases of papillary thyroid carcinoma in thyroglossal duct cyst (TDC) were compared to those of 3 cases of adenoma in TDC and 2 cases of benign TDC. The neck masses of the subjects with benign TDC grew slowly, whereas those of 2 patients with papillary carcinoma and 1 of the patients with adenoma grew rapidly (especially those with carcinoma). On the other hand, one case of carcinoma, and two cases of adenoma in TDC were diagnosed incidentally. Benign TDC had an anechoic pattern at US, whereas the cysts containing carcinoma and adenoma showed the presence of a mural nodule at US. Microcalcifications in the mural mass were present in one patient with carcinoma. The 3 patients with carcinoma in TDC underwent total thyroidectomy. The histology was negative in all 3 patients for thyroid cancer and thyroid nodules. However, in 2 of them it revealed the carcinoma invading the cyst wall and adjacent tissues, 1 of which also exhibited 2 metastatic lymph nodes in the central neck area. The cases reported illustrate the utility of enhancing one's clinical suspicion of carcinoma in patients bearing TDC, even when incidentally discovered. In particular, rapid growth of the cystic mass, and the presence of a mural nodule on US, especially with calcifications, must raise the physician's suspicion for a cancer arising in TDC.