In pathological states, the serum thyroglobulin (Tg) concentrations are generally high. Therefore, a serum assay of Tg levels is not useful for the differential diagnosis between benign or malignant disease in the preoperative period. Serum Tg measurements are a suitable marker in the follow-up of patients with differentiated thyroid carcinoma (DTC) during the postoperative period. After total thyroidectomy, serum Tg concentrations were found to be undectable in subjects without evidence of residual thyroid tissue or metastases; however, detectable serum Tg levels in subjects on and off thyroid hormone suppressive therapy indicate the presence of residual or metastatic thyroid tissue. An increase in serum Tg levels during thyroid stimulating hormone (TSH) suppression indicates that further investigations are necessary.