In recent studies of patients with differentiated thyroid cancer (DTC), an association between the persistence of tumor and the presence of circulating anti-thyroglobulin antibodies (TgAbs) have been described. The aim of the present study was to evaluate TgAb variations before and after total thyroid ablation and to correlate TgAb levels to the outcome of disease. Forty-three patients with DTC were studied (35 female, 8 male; 33 patients had papillary cancer and 10 follicular cancer). Tumor was intrathyroid in 20 cases, had spread to the lymph nodes in 19 and to the lungs in 4. All patients underwent total thyroidectomy and 131I therapy, and were then treated by suppressive doses of L-thyroxine. After a mean follow-up of 3.55 yr, TgAbs became undetectable in 24 patients (all were considered tumor-free), whereas TgAbs remained elevated in 19 cases. In 5 of these 19 patients, disease progression or persistence was documented (to the lymph nodes in three and to the lungs in two). TgAb levels were higher in patients with persistent disease in comparison with those tumor-free. Serum thyroglobulin (S-Tg) results were only elevated in the two patients with persistent disease in the lungs. Our data suggest that TgAbs determination may give some additional information to the follow-up of patients with DTC: the disappearance of TgAbs after therapy seems to represent a favorable prognostic factor, while the persistence of circulating TgAbs, particularly at high levels and in the absence of detectable S-Tg, may be representative of disease.