Hypercalcemia has been described as a possible complication of many pediatric malignancies. Here, we report an 8-month-old non-Down syndrome infant with acute megakaryocytic leukemia and severe hypercalcemia at presentation. A review of the literature reveals that this is the first case of hypercalcemia complicating acute megakaryocytic leukemia reported in the pediatric literature. His initial workup, and the course of management and outcome, is described in detail. Though the etiology of this complication remains unclear, our experience suggests that early institution of chemotherapy along with supportive care is the best treatment for control of hypercalcemia.