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Initial evaluation of an isolated elevation of alkaline phosphatase (ALP) should include repeat testing to confirm elevation, and a history and physical examination to evaluate for causes such as malignancy, congestive heart failure, hyperthyroidism, and renal disease. Most patients (52%) will have normalized levels of ALP within 3 to 12 months. A gamma-glutamyl transferase (GGT) or ALP isoenzyme will help identify the source of the ALP elevation. For bone sources, investigate for vitamin D deficiency, primary hyperparathyroidism, or Paget's disease. For hepatic sources, a liver ultrasound, antimitochondrial antibody, antinuclear antibody, and antismooth muscle antibody should be obtained, with further testing as appropriate (SOR: C, case series, narrative review, and consensus guideline).