Production of 1,25-dihydroxyvitamin D (1,25(OH)2D) is normally tightly regulated. Hypercalcemia, however, can result from overproduction or under-metabolism of 1,25(OH)2D. Several disorders are associated with 1,25-dihydroxyvitamin D-mediated hypercalcemia. These can be categorized into congenital or acquired disorders. Acquired ectopic overproduction of 1,25(OH)2D can be subdivided into malignant or nonmalignant diseases. Nonmalignant disorders can be further classified into infectious or noninfectious granulomatous conditions, such as tuberculosis and sarcoid, respectively. This chapter provides an overview of vitamin D production and metabolism, as well as the presentation, etiology, and diagnosis and treatment of hypercalcemia related to benign 1,25(OH)2D-mediated hypercalcemia.