Microsatellite instability (MSI) is a phenomenon characterized by small deletions or insertions within short tandem repeats in tumor DNA compared to matching normal DNA. Approximately 15% of all colorectal cancers (CRC) were found to be microsatellite instable, while MSI is a characteristic of more than 90% of tumors of patients with Lynch syndrome. Patients with MSI tumors have favorable prognosis and do not benefit from adjuvant chemotherapy with fluorouracil. Besides, MSI status of tumors is a prescreening step in detection of patients with Lynch syndrome. For determination of MSI we have developed a new multiplex PCR system with a set of five quasimonomorphyc mononucleotide markers and DHPLC analysis. Our subsequent strategy for screening of Lynch syndrome which has based on solely molecular genetic knowledge (methylation of MLH1 promoter and mutation analysis of MMR genes) has increased mutation detection rate from approximately 65% to 87% and has enabled to identify new patients with Lynch syndrome. Lynch syndrome is the most common autosomal dominant inherited predisposition for colorectal cancer. Carriers of the mutation have 70-80% life-time risk to develop Lynch syndrome, so there is the need to determine who of the relatives in the Lynch syndrome family inherited the mutation. Genetic counseling and genetic testing of relatives at risk, together with surveillance and prevention enable that the disease is detected in earlier curable stages what is connected with decreased cost for medical treatment and most importantly with better survival of patients.