A 55-year-old woman with stage IV-B nodular sclerosing Hodgkin's lymphoma presented to the emergency department with fever and lethargy of 12 hours' duration. The patient developed massive intravascular hemolysis secondary to Clostridium perfringens sepsis and cardiac arrest unresponsive to transfusions and cardiac pulmonary resuscitation, and died within 4 hours of presentation. The differential diagnosis of massive intravascular hemolysis, as well as the pathogenesis and treatment of C perfringens-induced hemolysis, are discussed.