Three cases of cardiotoxicity manifested by chest pain, tachycardia, respiratory distress, and electrocardiographic changes simulating acute myocardial infarction or ischemia were observed during the course of combination chemotherapy with etoposide, cisplatin, and continuous infusion of 5-fluorouracil in patients with advanced non-small cell lung cancer. There was no cardiac enzyme elevation. A similar but rare clinical syndrome has been described in association with 5-fluorouracil infusion as a single agent or in combination with other chemotherapeutic agents. We describe the cases and review their possible pathogeneses and clinical implications.