Our findings provide novel insight into the genetic screening of CRC patients in the era of multi-gene panel. Universal germline testing for cancer susceptibility genes should be recommend among all CRC patients diagnosed under age 70 years. It could discover substantially more individuals with hereditary cancer syndromes who would benefit from enhanced surveillance and tailored treatment. The testing panel could be optimized according to age of onset of CRC. A broad panel including genes from the additional set might be recommended to CRC patients older than 40 years to increase pathogenic variant detection rate and clarify inheritance risks. (By Wu Jiang, https://jmg.bmj.com/content/early/2021/02/09/jmedgenet-2020-107230 )