Aim:Pathology of Colorectal Cancer (CRC) is associated with environmental factors, food habits, lifestyle as well as genetic causes. Different study revealed sporadic cases of CRC accounting to approximately 60% of CRC with Microsatellite Instability observed in 7 to 20% of all sporadic cases. This study was aimed to determine the pathological spectrum of CRC in Barak valley (constitute district Silchar, Karimganj and Hailagandhi) and secondly to correlate the histopathological spectrum with MSI marker protein MLH1, MSH2 and MSH6 by Immunohistochemistry (IHC). Materials and Methods:A total of 54 CRC cases were assessed in the Department of Pathology out of all colectomy specimen and /or biopsy sample collected from the Department of Surgery, during the period from July 2013 to June 2014. IHC was done in paraffin embedded tissue containing carcinoma in total 32 cases with MLH1, MSH2 and MSH6. Results:The mean age of CRC was 49.31 yrs with male to female ratio of 2:1. Rectum was the most common site of CRC (55.55%) and colon cases together constituted 44.45%. Histopathologically adenocarcinoma constituted 90.74% of which moderately differentiated constituting 53.70%. IHC detected 6 out of 32 cases showing loss of expression for one or more of MLH1, MSH2 and MSH6 (18.75%). Tumors with loss of expression for MLH1 was significantly associated with right sided CRC (p = 0.00363) and with poorly differentiated, mucinous and signet ring cell carcinoma by morphology (p < 0.0001). Conclusion: 18.75% of sporadic CRC showed loss of expression of MMR protein. Use of IHC can add to determine cases with different clinical and morphological characteristics for further prognosis.