A 40-year-old previously healthy woman was admitted to the Service of Plastic Surgery in February 2000 because of an enlarging anterior midline neck mass she had noted some months before. In the previous 2 months the neck mass had been rapidly growing in size. Medical history included a cerebral trauma owing to a car accident, depression treated with fluoxetine and uterine fibroma. The patient had not been previously exposed to radiation or other known carcinogens. Familiar medical history was negative for thyroid gland or neoplastic diseases. Physical examination revealed a painless well-demarcated mass of about 6 cm localized in the midline of the neck above the thyroid gland covered by skin without any signs of inflammation and/or trauma. The thyroid gland was apparently normal in size and consistence and no significant cervical adenopathy was found at physical examination. At entry serum chemistry tests, electrocardiagram and chest X-rays were normal. A neck ultrasonography identified a 4 cm cyst above a slightly enlarged thyroid gland without any significant alteration. A Sistrunk surgical procedure was then performed and a mass of 5 cm was removed including the entire duct from the gland to the level of the foramen cecum and the middle portion of the hyoid bone. A small 1 cm wide lymph node close to the cyst was also surgically removed. Post-operative follow-up was uneventful. Gross examination of the surgical specimen showed a cystic mass of about 3 cm in greatest dimension with a smooth external surface. Microscopic examination showed the presence of papillary carcinoma with small areas of follicular carcinoma inside the thyroglossal duct cyst and metastatic disease in the adjacent lymph node. Further staging with neck sonogram showed an enlarged thyroid gland with a pattern suspicious for neoplastic disease subsequently confirmed by fine-needle aspiration biopsy. CT scan failed to identify distant metastatic disease. The patient underwent total nerve-sparing thyroidectomy with neck lymphoadenectomy. No significant post-surgical complications were recorded and the surgical wound healed regularly. Pathological examination showed a multinodular, moderately differentiated papillary and follicular carcinoma of the thyroid gland with focal invasion of the capsule and metastases in four neck lymph nodes. The main neoplastic nodule has a diameter of 1.8 cm. Post-operative staging according to the TNM classification was pT4b N1a M0. Surgical procedures were followed by iodine scan and radioactive iodine therapy with 131I ablation. Thyroid hormone replacement therapy was given regularly. In May 2003 evidence of iodine positive metastatic neck nodes was confirmed by fine-needle aspiration biopsy. Thyroglobulin levels were very high (355 ng/ml). The patient was rechallenged with 131I radioactive iodine therapy. To date the patient is still alive after 4 years.