The most common paraneoplastic syndrome, hypercalcemia of malignancy accounts for 40% of all hypercalcemia. Of cancer pts with hypercalcemia, 80% have humoral hypercalcemia mediated by parathyroid hormone–related peptide; 20% have local osteolytic hypercalcemia mediated by cytokines such as interleukin 1 and tumor necrosis factor. Many tumor types may produce hypercalcemia (Table 76-1). Pts may have malaise, fatigue, confusion, anorexia, bone pain, polyuria, weakness, constipation, nausea, and vomiting. At high calcium levels, confusion, lethargy, coma, and death may ensue. Median survival of hypercalcemic cancer pts is 1–3 months. Treatment with saline hydration, furosemide diuresis, and pamidronate (60–90 mg IV) or zoledronate (4–8 mg IV) controls calcium levels within 2 days and suppresses calcium release for several weeks. Calcitonin (2–8 U/kg) may be useful if rapid action is needed. Oral bisphosphonates can be used for chronic treatment. In the setting of hematologic malignancies, hypercalcemia may respond to glucocorticoids.