Few cases exist in which the production and secretion of PTH by malignant nonparathyroid tumors have been authenticated. A 69-yr-old man developed hypercalcemia complicating a primitive neuroectodermal malignancy that was widely metastatic. The serum level of intact PTH was markedly increased by immunoradiometric assay (90-290 ng/L; normal, 10-65 ng/L). The serum level of a PTH-related protein was also increased (19-20 ngeq/L; normal, < 10 ngeq/L). Exploration of the neck and mediastinum at two operations revealed four normal parathyroid glands. Extracts of the metastatic tumor contained immunoreactive PTH and transcripts of both the PTH and PTH-related protein genes. Thus, hypercalcemia in this patient was associated with production of PTH by a nonparathyroid malignancy.