BACKGROUND: Hypercalcemia and severe osteolytic lesions are rare complications of acute lymphoblastic leukemia (ALL) in childhood, and those cases share similar clinical features. Similarly, hypercalcemia is a rare feature in adult ALL. Here, we report an uncommon case of an adult patient with relapsed precursor B ALL (pre-B ALL) who developed multiple osteolytic lesions and hypercalcemia.CASE DESCRIPTION: A 24-year-old male patient, diagnosed with pre-B ALL, was admitted in our hospital due to severe lumbar pain. After reviewing laboratory, radiological and clinical findings, the patient was diagnosed as having relapse of a mixed phenotype acute leukemia, according to bone marrow aspiration (9% blasts) and cytogenetic analysis, with multiple osteolytic lesions in all lumbar vertebrae, sacrum and ilium and severe hypercalcemia (13.3 mg/dL). Thus, FLAG-IDA rescue therapy and hydration plus furosemide, corticoids and bisphosphonates were administered. Despite initial amelioration, his hematological condition deteriorated and he died due to severe sepsis as a result of severe immunosuppression.CONCLUSION: Two possible mechanisms have been suggested for hypercalcemia in hematological malignancy, either the leukemic infiltration or the paraneoplastic production of a variety of humoral factors and proinflammatory cytokines. However, hypercalcemia and severe osteolytic lesions are rare features in ALL adult patients and their combination may be indicator of poor prognosis. Hippokratia 2015, 19 (1): 78-81.