Background: Colorectal cancer (CRC) is one of the most common cancers worldwide. Approximately 15% of CRCs have microsatellite instability (MSI), which is caused by a dysfunction of the DNA mismatch repair (MMR) genes. The histopathological features have been applied to predict high frequency MSI (MSI-H) in CRCs, and we investigated this association with MSI-H and the histopathological features. Materials and methods: Fifty-four tumors were evaluated based on nine histopathological features associated with MSI-H. DNA was extracted and prepared from the FFPE of tumors and normal colon tissue. Five microsatellite markers (BAT25, BAT26, D2S123, D5S346, and D17S250) were screened. Results: Of the 54 cases, 38 (70.4%) were between 50-60 years old, and 16 (29.6%) were younger than 50 years. Tumors mainly presented in the left-side colon (40 cases, 74.1%). MSI-high (MSI-H) was found in 7 cases, MSI-low (MSI-L) was found in 7 cases, and the rest were microsatellite stable (MSS). The majority of CRC with MSI-H showed a Crohn-like lymphocytic reaction, mucinous features, tumor grade 2, and tumor-infiltrating lymphocytes. Only the mucinous component was significantly associated with the MSI-H (P < 0.05). Conclusion: The initial prevalence of MSI-CRCs in our study (via 5 microsatellite markers) was similar to previous studies. Some histopathological features helped to guide the MSI testing. Even though only the mucinous features were related to the MSI-H status, none of MSI-H CRCs lacked any of the of 9 selected histopathological features. Our study was limited by selected age groups and a small sample size. Further studies with more samples including all age groups should be performed to demonstrate the usefulness of the histopathological features in predicting the MSI in CRC.