Tumor lysis syndrome (TLS) is a life-threating hematologic emergency caused by massive lysis of tumor cells into the blood stream. TLS can be prevented and treated with rasburicase. Rasburicase-induced hemolysis and methemoglobinemia is a rare but serious complication. Screening for G6PD should be considered for patients at higher risk for G6PD deficiency who may be also at high risk for TLS on the basis of clinical parameters. G6PD level in G6PD-deficient patients may be normal during an acute hemolytic episode and may not help to clarify the diagnosis at the time of presentation. The characteristic peripheral blood smear findings of 'bite' and 'blister' cells representing oxidative damage to red blood cells can help to quickly establish the diagnosis of G6PD deficiency-related hemolysis. The treatment of an acute hemolytic episode in a patient with G6PD deficiency requires avoiding the source of oxidative stress and using transfusion support as needed.