Humoral hypercalcemia associated with malignancy has rarely been reported in exocrine pancreatic cancer. We report a patient with cancer of the exocrine pancreas who presented with hypercalcemia which did not respond to indomethacin. Her serum levels of parathyroid hormone and vitamin D derivatives were low. Technetium diphosphonate bone scan revealed no evidence of bone metastasis, a finding which was confirmed at autopsy. On light microscopy, histological classification of the tumor was moderately differentiated tubular adenocarcinoma. The electron microscopic study, however, revealed a few zymogen-like granules containing cancer cells lying between ductal-type cancer cells. A review of humoral hypercalcemia in cancer of the exocrine pancreas is presented. A humoral factor(s) other than parathyroid hormone, prostaglandin E, and vitamin D derivatives is considered responsible for hypercalcemia in this patient.