This study examines the cancer risks in individuals with hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome, caused by germline mutations in DNA-mismatch-repair genes. The research analyzed 1,763 family members from 50 genetically diagnosed HNPCC families, categorizing them based on their genetic status as mutation carriers, non-carriers, or individuals at 50 or 25% risk of being carriers. The study compared cancer incidence in these groups with that of the general Finnish population. The results showed significantly increased standardized incidence ratios (SIR) for several cancers in mutation carriers, including colorectal, endometrial, ovarian, gastric, biliary tract, uro-epithelial, kidney, and central-nervous-system tumors. The SIR for colorectal cancer was higher in men than in women, while endometrial cancer incidence in women exceeded that of colorectal cancer. The cumulative cancer incidence for colorectal and endometrial cancers was 82% and 60%, respectively, in mutation carriers, compared to much lower rates in the general population. The study highlights the need for screening for extra-colonic cancers in HNPCC families, as the tumor spectrum associated with germ-line mutations of DNA-mismatch-repair genes involves 8 or more organ sites. While screening for endometrial cancer is justified due to its high cumulative incidence, the effectiveness and cost-effectiveness of screening for other cancers, such as gastric and ovarian, remain questionable. The study also emphasizes the importance of genetic testing for HNPCC families, as it allows targeted cancer prevention and screening for mutation carriers, reducing unnecessary cancer risk for non-carriers. The findings underscore the importance of genetic counseling and tailored screening strategies for HNPCC families, as the risk of various cancers is significantly higher in mutation carriers. The study provides valuable insights into the cancer risks associated with HNPCC and highlights the need for further research to develop effective screening and prevention strategies for these individuals.This study examines the cancer risks in individuals with hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome, caused by germline mutations in DNA-mismatch-repair genes. The research analyzed 1,763 family members from 50 genetically diagnosed HNPCC families, categorizing them based on their genetic status as mutation carriers, non-carriers, or individuals at 50 or 25% risk of being carriers. The study compared cancer incidence in these groups with that of the general Finnish population. The results showed significantly increased standardized incidence ratios (SIR) for several cancers in mutation carriers, including colorectal, endometrial, ovarian, gastric, biliary tract, uro-epithelial, kidney, and central-nervous-system tumors. The SIR for colorectal cancer was higher in men than in women, while endometrial cancer incidence in women exceeded that of colorectal cancer. The cumulative cancer incidence for colorectal and endometrial cancers was 82% and 60%, respectively, in mutation carriers, compared to much lower rates in the general population. The study highlights the need for screening for extra-colonic cancers in HNPCC families, as the tumor spectrum associated with germ-line mutations of DNA-mismatch-repair genes involves 8 or more organ sites. While screening for endometrial cancer is justified due to its high cumulative incidence, the effectiveness and cost-effectiveness of screening for other cancers, such as gastric and ovarian, remain questionable. The study also emphasizes the importance of genetic testing for HNPCC families, as it allows targeted cancer prevention and screening for mutation carriers, reducing unnecessary cancer risk for non-carriers. The findings underscore the importance of genetic counseling and tailored screening strategies for HNPCC families, as the risk of various cancers is significantly higher in mutation carriers. The study provides valuable insights into the cancer risks associated with HNPCC and highlights the need for further research to develop effective screening and prevention strategies for these individuals.