L-Asparaginase is an effective drug in childhood acute lymphoblastic leukemia (ALL) and it has become an important component of most childhood ALL regimens with administration in induction, intensification, and maintenance phases of treatment. L-Asparaginase is associated with side effects occurring either in a dose or time-dependent fashion or as hypersensitivity reactions. Some well-known toxicities in asparaginase-containing regimens are hypersensitivity/allergy and thromboembolic events. When asparaginase and steroids are used together, mild hyperlipemia is reasonably common. As some published studies show, this abnormality is often underdiagnosed. Hyperlipemia rarely constitutes a clinical problem; however, when triglyceride elevation is greater than 1000 mg/dL, the risk of pancreatitis is increased. We report the case of a young female presenting with acute severe hypertriglyceridemia (9250 mg/dL) during intensification phase of ALL, with neurologic symptoms but without the development of pancreatitis. She was successfully managed with 1 single run of plasmapheresis.