Anthracycline cardiotoxicity is cumulative and can cause congestive heart failure. The cardiotoxicity caused by 5-fluorouracil (5-FU) is acute and is usually observed during the first cycle of chemotherapy. We present the case of a female patient operated on for colorectal cancer and receiving her first postoperative chemotherapy cycle. Three hours after the initiation of continuous 5-FU infusion she developed signs of acute heart failure (AHF) and pulmonary edema. The patient did not have any previous history of heart disease. Symptoms resolved 24 hours from the onset of the episode after the initiation of the relevant emergency therapy. One of the most common symptoms related to 5-FU cardiotoxicity is chest pain. In case of such a toxicity treatment should be switched to another antineoplastic agent.