Pancreas cancer-associated antigen (PCAA), primarily isolated from the ascites of pancreatic cancer (PC) patients, is strongly positive in PC, colon cancer and normal colonic mucosa. In immunohistochemical staining of tumor tissues with antibodies, medullary thyroid carcinoma (MTC) was no less strongly positive for PCAA than PC, and we studied its details. Antibodies to PCAA, calcitonin and CEA were used in the immunostaining of normal thyroid tissues and thyroid tissues from patients with adenomas, MTC, papillary carcinomas, and follicular carcinomas. The PCAA from the liver metastases of MTC was studied for molecular weight and antigenicity in comparison with the PCAA from the ascites of PC patients. Serum levels of PCAA were determined in MTC patients. Of 11 patients with MTC, PCAA, calcitonin and CEA were studied immunohistologically and positive in 10, 11 and 10 patients, respectively. The PCAA from the metastases had a molecular weight of about 700,000, and was immunochemically identical to that from the ascites of PC patients. Serum levels of PCAA were elevated in 4 of 6 MTC patients. The thyroid tissues from the MTC patients, familial or non-familial, were as strongly positive for PCAA as for calcitonin and CEA. It was antigenically identical to that of PC origin, and positive in the serum of MTC patients.