This study is an attempt to unify the evaluation of patients with well-differentiated thyroid cancer after ablative therapy. As such serum thyroglobulin determinations on and off thyroid hormone (T4) therapy and iodine 131 total body scans were examined in 53 patient studies. No metastases were found in patients whose thyroglobulin value was undetectable (less than 1 ng/ml). Values during T4 therapy that were detectable, even as low as 4.2 ng/ml, were occasionally associated with metastases. After T4 withdrawal, thyroglobulin value and scan were obtained. Neither metastasis nor clinically detectable cancer was found in patients whose thyroglobulin value was less than 10 ng/ml while off T4. Conversely, a value greater than 10 ng/ml was often associated with documented metastases even when the scan was negative. In summary, a thyroglobulin value less than 1 ng/ml during T4 therapy or less than 10 ng/ml off T4 therapy suggests successful therapy and a routine scan could be avoided unless clinically indicated. However, a value greater than 10 ng/ml suggests the presence of metastasis despite a negative scan. Thyroglobulin determination substantially improves the management of these patients.