Approximately 5-10% of all colorectal carcinomas arise from cancer predisposition syndromes caused by heterozygote germline mutations in post-replicative DNA mismatch repair (MMR) genes. In contrast to gastrointestinal polyposis syndromes, carcinomas in these patients do not occur on the background of increased numbers of polyps and hence are refered to as hereditary non-polyposis colorectal cancers (HNPCC). Six different MMR genes, MSH2, MSH3, MSH6, MLH1, MLH3 and PMS2, have been identified in the human genome. In the majority of HNPCC patients, heterozygote germline mutations are present in the MSH2 or MLH1 gene. Detection of mutations by conventional sequencing technology is expensive and labor intensive due to the complex intron and/or exon structures. In this study, we therefore have explored whether capillary electrophoresis-based single strand conformation polymorphism (SSCP-CE) provides a reliable means for mutation screening. We have tested different MLH1 mutations in exons 9 and 16 and find that SSCP-CE produces reliable electrophoretic patterns that allow recognition of wild-type alleles, microdeletions and point mutations. In summary, SSCP-CE provides a rapid, automated, and cost-effective technology for MSH2 and MLH1 mutation screening and will facilitate genetic diagnostics for HNPCC patients.