5-fluorouracil (5-FU) and its prodrug capecitabine are frequently prescribed in oncology. While usually well tolerated, toxicity can be severe, and even life-threatening. A dihydropyrimidine dehydrogenase (DPD) deficiency can cause severe toxicity. Current testing for DPD deficiency does not meet the criteria for a routine screening test prior to 5-FU therapy. A case study of a fatality secondary to capecitabine toxicity is reviewed and literature is examined regarding general screening for DPD deficiency.