Hypercalcemia is a relatively common clinical finding; prevalence rates are 1.4 to 3.0 per cent in hospitalized and general clinical populations. Malignancy is the major cause of hypercalcemia in hospital patients, whereas primary hyperparathyroidism (HPT) is the major cause in ambulatory patients. In both hospitalized and ambulatory patients, however, there are many other causes of hypercalcemia, and numerous procedures have been proposed to aid in the differential diagnosis. Unfortunately, no single test is truly diagnostic. The work-up for hypercalcemia requires an integrated knowledge of the strengths and weaknesses of the various procedures as well as an understanding of the various clinical presentations associated with hypercalcemia.