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The dynamics of morbidity and mortality in colorectal cancer (CRC) has changed little in recent years and consistently remains at a high level. The carcinogenesis of this type of tumors includes a large number of genetic disorders and epigenetic changes, which show a number of features specific for this nosology, providing the basis for the first consensus classification of molecular subtypes for colorectal cancer. One of the main mechanisms chosen as crucial for this classification is the microsatellite instability (MSI) caused by defects in the DNA Mismatch Repair System (MMR). The clinical significance of this CRC molecular profile parameter is hard to overestimate. Over the past three decades, the MSI and MMR have been actively studied for prognosis evaluation, determination of need and selection of appropriate adjuvant chemotherapy scheme for CRC. Despite the significant accumulation of clinical and experimental study data, currently the prognostic value of this parameter is still not well defined with reference to CRC adjuvant treatment strategies, and the released data remain controversial. The purpose of this analytic review is to analyze the current status of MSI and MMR in the setting of adjuvant treatment of CRC patients from a perspective of evidence-based medicine.