In families with suspected or clinically diagnosed hereditary nonpolyposis colorectal cancer (HNPCC), genetic testing for mutations in one of several mismatch repair (MMR) genes is used to determine whether an individual has an increased risk for colorectal cancer or other HNPCC-associated cancers, improving cancer risk assessment in these individuals and families. Testing may also include microsatellite instability (MSI) analysis and/or immunohistochemical staining of the tumor tissue of an affected family member as initial screen(s) before germline mutation testing is performed.