Background: Colorectal cancer is one of the leading causes of cancer death in both developed and developing nations. It is the third most common type of cancer and the fourth leading cause of cancer-related deaths worldwide. Ezrin is involved in maintaining cell structure and cell motility. Expression levels of the ezrin gene correlate with numerous human malignancies. Material and Methods: Ezrin expression was evaluated in fifty one cases of colorectal carcinoma by using two methods; objective and quantitative method to determine the statistical relation between ezrin objective analysis score and clinicopathological parameters and to do a comparative study between both methods of analysis. Results: Ezrin was expressed in 92.2% of cases, and it showed a statistical significant relation with tumor grade. A statistically significant relation was found between ezrin objective analysis score and ezrin quantitative analysis score (P-value <0.05). A strong positive Pearson correlation exists between both methods of analysis (R=0.868). Conclusion: Ezrin has a role in colorectal cancer progression and it might provide clinically valuable information in predicting the behavior of colorectal cancer. Digital pathology offers the potential for improvements in quality, efficacy and safety. It will be necessary to carry out similar studies on a larger sample size in order to elucidate the possible prognostic significance of ezrin in colorectal carcinoma and ensure the ability of digital pathology to transform the practice of diagnostic pathology.