Seventy‐three cases of hyperparathyroidism associated with malignant tumors of nonparathyroid origin, including 9 previously unpublished cases, are reviewed. Clinical correlation with tumor treatment and recurrence suggests that the tumors elaborate a substance with parathyroid hormone activity. Immunochemical and physicochemical data indicate a close similarity to, or identity with, parathyroid hormone. The hypothesis is advanced that the mechanism of production of a substance with parathyroid hormone activity by nonparathyroid neoplasms is a process of derepression of the coded genetic sequence that specifies synthesis of parathyroid hormone. This hypothesis leads to the predictions that such neoplastic cells are prepared with the protein synthetic machinery to produce the specified polypeptide structure and that the most probable polypeptide sequence for the substance is one identical with parathyroid hormone. An unexplained histologic association of chemical hyperparathyroidism with squamous cell and of hyperadrenocorticism with oat cell carcinoma of the lung is emphasized.