This retrospective study was conducted to evaluate the incidence and prognostic significance of humoral hypercalcemia in 218 renal cell carcinoma patients during the last 20 years. Of 218 patients 20 (9.2%) were hypercalcemic, with serum calcium levels ranging from 10.7 to 16.0 mg./dl. The respective incidence of humoral hypercalcemia was 3% in patients with stage I, 5.9% with stage II, 14.1% with stage III and 18.9% with stage IV disease without bone metastasis. The survival curves between the hypercalcemic and eucalcemic groups among stages I to III cancer patients showed no statistical significance (p greater than 0.05). The survival curve deteriorated significantly in stage IV cancer patients with humoral hypercalcemia (p less than 0.005), with a median survival of 45.0 +/- 39.7 days versus 286.4 +/- 27.6 days in eucalcemic patients. No specific correlation was found between pathological cell type and humoral hypercalcemia.