An autopsy case of prostaglandin E-producing hepatocellular carcinoma with hypercalcemia is presented in this article. A 72-year-old man showed high serum calcium levels (14.2 to 17.3 mg/100 ml) and hypophosphatemia. The plasma level of immunoreactive parathyroid hormone was below the normal range. Administration of oral indomethacin 50 mg daily was effective in decreasing the serum calcium concentration. However, this effect lasted only 5 days, after which it returned to pretreatment levels. The patient died in a hypercalcemic coma. By an autopsy, hepatocellular carcinoma was found in the right lobe of the liver. However, no obvious bone metastases nor abnormalities in the parathyroid glands were detected. The immunoreactive prostaglandin E level assayed in the neoplastic tissue (2278 ng/g) was significantly high when compared with level in the nonneoplastic liver tissue (194 ng/g). The production of prostaglandin E by the tumor itself appears to be the most likely mechanism for the hypercalcemia in this patient.