Background: Colorectal cancer is a foremost global health concern. It is the third most common cancer in adults a!erlung cancer and breast cancer worldwide. The theory that cancer originates from tumor cells, named cancer stem cells, they are important in the maintenance of the tumor, invasion, metastasis and therapeutic resistance. Among CSC markers, CD44 and OPN are twoof the most inves%gated colorectal CSC markers and their proteins are introduced as the subpopula%on with agreater tumorigenicity. This study aiming assessing the immunohistochemical expression of CD44 & OPN incolorectal adenomas & CRCs. And their rela%on between immunohistochemical expression of CD44 & OPNwith tumor di/eren%a%on (grading), lympho-vascular invasion, perineural invasion, desmoplasia and TNMstage. Methods: this is a retrospec%ve descrip%ve study that included Sixty paraffin embedded blocks from thepathology laboratory, Suez Canal University Hospital. Paraffin blocks included (14 cases of colorectalcarcinoma and 18 cases of colorectal adenoma). paraffin blocks reviewed for clinicopathological prognosticfactors and stained by CD44 & OPN, monoclonal antibodies by immunohistochemical method. Results: TheCD44 protein was overexpressed in 80% of CRC, while was positive (44.4%) in adenoma this difference was statistically significant. Also, in this study the difference between the expression OPN in CRC and adenomas was statistically insignificant. Conclusions: CD 44 is highly expressed in large number of CRC. It is also significantly more expressed in CRC than in adenomas, suggesting a role of CD 44 in CRC tumorigenesis and progression of adenomas into carcinomas. Our study also associated CD 44 over expressionwith both late TNM stage and lympho-vascular invasion.