The FDA updated the label for Genentech’s capecitabine (Xeloda) to include an explicit boxed warning recommending DPYD genetic testing before initiating therapy when clinically possible. The agency moved from ‘consider testing’ language to a directive stating patients should be tested for DPYD variants that cause complete dihydropyrimidine dehydrogenase (DPD) deficiency unless immediate treatment is required. The change follows years of advocacy from patient groups and discussions at an FDA–American Association for Cancer Research workshop earlier in 2025. The revision targets prevention of severe fluoropyrimidine toxicities—mucositis, neutropenia, diarrhea and neurotoxicity—which can be fatal in patients with DPD deficiency. Oncologists and guideline bodies such as the NCCN have already shifted toward recommending DPYD screening in some settings; the label update is likely to accelerate payer and institutional adoption of routine pre-treatment pharmacogenetic testing and to trigger implementation work in clinics and labs.