We report a case of severe hypocalcemia in a patient with prostate cancer and extensive metastatic bone disease. The hypocalcemia in this patient was most likely on the basis of extensive accretion of calcium into the bones. We further studied 112 patients with prostate cancer, 15 of whom were discovered to be hypocalcemic on the basis of serum total calcium measurement. Fourteen of these 15 patients had bone metastases. Serum total calcium, total protein, and albumin levels were significantly lower in patients with bone metastases (n = 61) than those without (n = 51). Hypocalcemia could be explained on the basis of hypoalbuminemia or renal failure in these patients. Plasma ionized Ca measurements were made in 47 of the total 112 patients. Only one patient with extensive bone metastases was found to be hypocalcemic on the basis of ionized calcium measurement. Therefore, apparent hypocalcemia based on total calcium measurement is common in patients with prostate cancer (14% of all and 23% of those with bone metastases), whereas true hypocalcemia based on ionized calcium determinations is unusual.