Background and Study Aims: Microsatellite instability pathway caused by loss of DNA “Mismatch Repair genes” (MMR) is responsible of Lynch Syndrome-related tumors and 10-15% of sporadical colorectal cancers. Although MSI-test is regarded as the golden standard for detection of “Lynch Syndrome-related tumors”, there are increasing evidence on similar analytic sensitivity of immunohistochemical evaluations. Patinets and Metods: We retrospectively evaluated 1002 colorectal tumors for loss of DNA MMR protein (MLH1, PMS2, MSH2, MSH6) immunohistochemically. The results were correlated with clinicopathological features and high level-microsatellite instability (MSI-H) related histological parameters. Results: MMR protein expression loss was observed in 9.8% of the cases. MLH1-PMS2 loss (53.2%) was the most common loss followed by MSH2-MSH6 (31.6%), isolated PMS2 loss (12%), and isolated MSH6 loss (2%). MMR deficiency was more frequent under 50 years-old (p<0.0001), in right colon tumors (p<0.0001), poorly differentiated tumors (p<0.0001), tumors with tumor infiltrating lymphocytes (p<0.0001), mucinous component (p=0.001), and medullary component (p<0.0001). Also MMR deficiency was less frequent in tumor with tumor budding (p<0.0001) and dirty necrosis (p<0.0001). The 5 years-survival rate was 55.7%. No significant correlation was found with MMR deficiency and survival. Conclusions: MMR deficiency was observed in 9.8% of the cases with distinct clinicopathological features. The results were consistent with previous studies. Unlike the literature, we did not find any statistically significant difference between MMR deficiency and prognosis.