Hypercalcemia is a well-recognized phenomenon in squamous cell carcinoma of the head and neck, but the incidence of hypercalcemia in this group of patients is not clear. We have reviewed the records of 166 patients with squamous cell carcinoma of the head and neck presented at the Boston VA Medical Center over a 2-year period (October 1981 to September 1983). Hypercalcemia (> 11 mg/dl), for which a benign etiology could not be identified, occurred in the clinical course of seven patients (4.2%). Of the hypercalcemic patients, 5/7 (71.4%) had advanced stage IV disease and serum calcium levels ranging from 11.2 to 15 mg/dl at presentation. The incidence of hypercalcemia in this stage IV group was 5/78 (6.4%). On the basis of concomitant serum alkaline phosphatase, x-ray films, and radionuclide bone scans in these patients, bone metastases or a humoral factor were felt to be the etiologic agent. Six of the seven patients died within 77 days of the onset of the hypercalcemia despite vigorous antihypercalcemic and chemotherapeutic measures, and the remaining patient is under chemotherapy at present. We conclude that hypercalcemia is a late manifestation of advanced squamous cell carcinoma of the head and neck and is an ominous prognostic sign. Hypercalcemia without bone metastases is presumably due to the production of ectopic parathormone (PTH)-like substances from the tumor. To control this hypercalcemia, the underlying tumor must be treated vigorously in conjunction with symptomatic treatment. It should be noted that of 166 patients not all have been followed to the end stage of their disease and, thus, the true incidence of hypercalcemia may be slightly higher than 4.2%.