BACKGROUND Malignant hypercalcemia is a rare finding in the pediatric population, even more rare in hematological malignancies, such as leukemia. CASE REPORT We present a case of a 6-year-old female patient who was diagnosed with acute lymphoblastic leukemia, with secondary hypercalcemia. She started chemotherapy following the IC-BFM ALL2002 protocol with simultaneous calcitonin, diuretics and aggressive hydration for hypercalcemia, and went into complete remission after the induction therapy. After 4 months of chemotherapy, she was diagnosed with relapse associated again with malignant hypercalcemia, and underwent chemotherapy with the relapse protocol. There was no response after the first 2 cycles, so we decided to start her on clofarabine. Due to the severe hypercalcemia and consecutive osteolysis, she developed several bone fractures and needed gypsum immobilization. We started her again on calcitonin, but she developed severe adverse reactions, so we found it necessary to start bisphosphonates, first zoledronic acid intravenously, and afterwards clodronate orally. Consolidation of bone fractures was achieved, but due to prolonged immobilization she developed bedsores, superinfected with Lichtheimia corymbifera. We started posaconazole orally, but she rapidly went into severe sepsis with multiple organ failure. The leukemia showed no response to chemotherapy, progressed rapidly, and the patient died. CONCLUSIONS Malignant hypercalcemia is associated with a poor prognosis in leukemia, and might need a more aggressive therapy.