Rasburicase is frequently used in tumor lysis syndrome (TLS). Although it is very well tolerated, it can cause severe oxidative hemolytic anemia and methemoglobinemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We report another case of rasburicase-induced methemoglobinemia in a patient with previously unrecognized G6PD deficiency and review the cases of methemoglobinemia and oxidative hemolysis reported in the literature to date. Patients from ethnicities in which G6PD deficiency is prevalent at high risk of TLS should be screened for G6PD deficiency prior to administration of rasburicase where practical. Asymptomatic decrease in oxygen saturation by oximetry and cyanosis are signs of methemoglobinemia; patients recover with conservative measures including supplemental oxygen and packed red cell transfusion.