Fluoropyrimidines remain some of the most used chemotherapeutics, despite the appearance in the therapeutic arsenal of targeted therapy and immunotherapy. Fluropyrimidines related cardiotoxicity is an undesirable adverse event and affects almost 20% of patients. The mechanisms of fluoropyrimidine toxicity are closely related to deficient allelic variants of DPYD, but considering the low penetrance and interindividual variability, not all adverse reactions are explained by their presence. In this case, we report a patient with recurrent fluoropyrimidine toxicity without a deficient allelic variant and how this case was managed by the oncologist and cardiologist, considering the need to use fluoropyrimidine in the treatment.