Patients with metastases from differentiated thyroid carcinoma have a good chance of long-term survival when the diagnosis is prompt and appropriate therapy is applied early. This is also true for patients with metastases in the bone, taking into account that an appropriate therapy, usually 131-I, may be palliative in some cases. This study investigates whether serum thyroglobulin (Tg) measurement in patients with cold thyroid nodule and metastases from an unknown primary site could help identify a differentiated thyroid carcinoma. The results obtained show that Tg measurements is a useful adjunctive test when used with fine-needle aspiration biopsy. In particular, very high Tg levels point to metastatic thyroid cancer, whereas lower levels do not help determining whether metastatic cancer is of thyroid origin or not.