Cyclophosphamide is a chemotherapeutic agent with the potential to cause pulmonary toxicity, most commonly in the form of diffuse alveolar damage. Cyclophosphamide-induced pulmonary toxicity is extremely rare and often difficult to recognize because of presence of confounding factors, including use of other cytotoxic drugs, radiation pneumonitis, oxygen toxicity, pulmonary infections, and malignancies. The lung toxicity caused by cyclophosphamide is accelerated when cyclophosphamide is combined with amiodarone, an antiarrhythmic agent also capable of lung toxicity. We describe a patient with non-Hodgkin's lymphoma who developed fatal pulmonary toxicity after a single dose of cyclophosphamide in the setting of long-term amiodarone use.