The impact of the unrecognized mutational dihydropyrimidine-dehydrogenase-gene-(DPYD)-status on high-grade CTC-AE-grades ≥ 3 (NCI-Common Terminology Criteria for Adverse Events, vs. 3.0) was assessed in patients with upper rectal cancer (inferior tumor margin ≥ 12 cm above the anal verge) treated with upfront surgery and 5-Fluorouracil (5-FU) based adjuvant chemotherapy (CTx). This evidence concerns the gene DPYD and neoplasm.