Acute severe hypophosphatemia can be life threatening and is associated with mortality and impaired cardiac and respiratory function. Several conditions including decreased absorption or increased urinary phosphate excretion, shifts from the extracellular to intracellular compartments, and phosphate consumption by rapidly proliferating cells are known to induce moderate to severe acute hypophosphatemia. Although hypophosphatemia and/or phosphate depletion in patients with acute or chronic myeloid leukemia have been reported in the literature, hypophosphatemia due to acute lymphoblastic leukemia (ALL) is very rare. We report a case of history of ALL complicated by life-threatening hypophosphatemia manifesting as generalized muscle weakness, fatigue, acute shortness of breath, and difficulty in standing up and walking for 3 days. Serum inorganic phosphate levels were consistently low (0.06 mmol/L). The patient was hospitalized and thought to have a relapsed ALL.Anticancer agents and oral phosphate (660 mg twice daily) were administered. On the second day of treatment, the patient began to improve, and the patient gradually fully recovered within 5 days.We suggested that this hypophosphatemia was induced by a shift of phosphorus into leukemic cells that rapidly replicated in the tissues and excessive cellular phosphate consumption by rapidly proliferating cells. Serum phosphate levels should always be monitored,especially in suspected life-threatening manifestation in relapsed ALL.