Histologic sections of squamous cell carcinomas of four hypercalcemic patients were investigated for the presence of parathyroid hormone (PTH)-like substance. None of the patients had clinical or radiographic evidence of bone metastases. The Sternberger-peroxidase-antiperoxidase-immunoperoxidase technique utilizing monospecific antibody to whole (1 to 84) bovine PTH demonstrated immunoreactive material in all cases. Electron microscopy of the four tumors revealed dense-core secretory granules resembling those seen in parathyroid chief-cell adenomas. The patients did not have elevated serologic levels of PTH or evidence of bone metastases; however, in two cases, osteoclastic bone resorption was seen in bone marrow biopsy specimens. All patients became normocalcemic after definitive tumor resection. The hypercalcemia associated with some nonmetastatic squamous cell carcinomas is associated with the production of PTH-like substance.