Five-fluorouracil (5-FU) and platins remain a first line treatment in oncology with a potential of cardiovascular toxicity. We identified two cases of acute severe cardiac toxicity treated with a combination of 5FU (different production batch) and platins at three months interval at two different institutions referred to our cardio-oncology services. Both cases had similar clinical presentation, favorable outcomes and identical cardiac magnetic imaging scans at follow-up. Mechanism was direct myocardial toxicity in the case with endomyocardial biopsy. Circulatory support as a bridge to recovery should be considered in the case of untreatable cardiogenic shock likely due to 5-FU.