Fluorouracil (5-FU) is a pyrimidine analog widely used in oncology. It is mainly used in the treatment of solid tumors. It is also used along with radiotherapy because of its radiosensitizing properties. As with all chemotherapy drugs, 5-FU is associated with adverse effects. Cardiotoxicity is one of them. It can present in a variety of ways and, sometimes, it can be lethal too. The reported case is of a 42-year-old male who presented with atypical chest pain after the first dose of 5-FU and was finally diagnosed with 5-FU-induced cardiotoxicity. His cardiac function normalized after the withdrawal of the drug.