A 24-year-old male presented with respiratory failure and superior vena cava (SVC) syndrome secondary to Burkitt's lymphoma with mediastinal mass causing tracheobronchial compression. Femoral-femoral veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) was initiated for hypercarbic and hypoxemic respiratory failure as well as cardiac tamponade. Multiple off-site transports to and from the cancer institute for chemotherapy and fractionated external beam radiation were required. Resultant tumor shrinkage allowed ECMO weaning and decannulation. The patient was discharged and returned to postgraduate education. Aggressive intervention with ECMO support permitted chemotherapy, radiation treatment, and ultimately a successful outcome in high-grade Non-Hodgkin's lymphoma (NHL), specifically if the respiratory failure is secondary only to extrinsic airway compression.