Pediatric patients with malignancies are at significant risk for complications from their underlying condition and medical therapy. Emergency medicine physicians must be quick to suspect life-threatening events, which can present insidiously. We describe a case of anaphylaxis and superior vena cava syndrome in an 18-year-old female patient after polyethylene glycol-conjugated asparaginase chemotherapy for acute lymphoblastic leukemia. Pertinent literature surrounding risk factors, diagnosis, and treatment is also reviewed. © 2008 by Lippincott Williams & Wilkins.