Mainstreaming—shifting genetic testing outside clinical genetics—can improve access, but requires evaluation to ensure consistent, high-quality care. This study assessed real-world implementation of mainstream cancer genetic testing across multiple centres and cancer types, incorporating both clinical and laboratory genetics perspectives. Practice was broadly aligned for common indications, including breast, ovarian, and prostate cancer. However, variability remained in areas with implications for resource use and care quality, including routine result turnaround time, negative-result management, and the extent of genetics-service involvement. These findings highlight opportunities to optimize mainstreaming and support more consistent, equitable cancer genetics care. (https://jmg.bmj.com/content/early/2026/09/21/jmg-2026-111749)