Four hundred thirty surgical and biopsy specimens of malignant thyroid tumors of 323 patients were analyzed by histologic and immunocytochemical examination for their thyroglobulin (TG) content. Almost 95% of the differentiated thyroid carcinomas of follicular origin contained immunoreactive TG. The authors could not demonstrate TG in anaplastic carcinomas. Postoperative follow-up and serum TG determinations were available for 111 athyroid patients. Serum TG was elevated in five patients with metastatic or recurrent moderately differentiated follicular carcinoma, in two patients with metastasizing papillary, and in one patient with anaplastic carcinoma. Four patients had detectable serum TG levels without clinical and radiologic evidence of recurrence or metastases. In addition to conventional histologic examination, immunocytochemical demonstration of TG is a reliable and valuable aid in the diagnosis, classification, and determination of the grade of differentiation of malignant thyroid tumors. From this the pathologist can provide a pathologic basis for postoperative patient management.Cancer 57:1145-1153, 1986.ANY DIFFERENTIATED thyroid carcinomas are M treated by near total thyroidectomy and administration of ablative doses of radioiodine. Secretion of thyroid-stimulating hormone (TSH) is suppressed by thyroxine replacement. The technique commonly used for detection of recurrent or metastatic disease is iodine 13 1 (I3'I) total body scan (TBS) at regular intervals. In order to stimulate iodine uptake by tumor tissue, the patients must discontinue thyroid medication for at least 10 days before examination and are subject to transient hypothyroidism, often with extreme fatigue, inactivity, and sometimes depression. With the development of sensitive raFrom, the