This study compared serum thyroglobulin measurement and whole-body scans in the post-surgical follow-up of patients with differentiated thyroid carcinoma. Thyroglobulin levels were measured in 61 patients receiving L-thyroxine therapy after thyroidectomy, and again after suspension of therapy, before performing a whole-body scan with iodine-131. The sensitivity, specificity, and accuracy of thyroglobulin levels, measured during L-thyroxine therapy, for diagnosis of tumor residue or metastases were then calculated and compared with results obtained by diagnostic whole-body scanning. Our data show that neither thyroglobulin levels nor whole-body scans alone can discriminate between patients with or without metastases. Sensitivity reached 95.7%, specificity 100%, and accuracy 96.7% if results of both procedures were also taken into consideration. We conclude that in the management and follow-up of patients with differentiated thyroid carcinoma both parameters need to be evaluated.