This nationwide French study of patients with LS supports a genotype–phenotype correlation. There were no path_PMS2 carriers in this cohort. Overall, the cumulative CRC risk by 70 years was 38% in men and 31% women. When analysed by genotype, the cumulative CRC risks were 46% for path_MLH1, 48% for path_MSH2 and 12% for path_MSH6. Median age at diagnosis of CRC also varied by genotype: 45 (range 15–90) years for path_MLH1, 44 (16–95) years for path_MSH2 and 54 (24–85) years for path_MSH6. This evidence concerns the gene MSH2 and colorectal carcinoma.