Background: Colorectal carcinoma considered the most worldwide concern and one of the major causes of morbidity and mortality rates. The cancer originates from a types of tumor cells, called cancer stem cells, they have important in the initiation of the tumor, invasion, metastasis, and therapeutic resistance. Among CSC markers, CD44 and OPN are two of the most investigated colorectal cancer markers and they are considered as the subpopulation with a greater tumorigenicity. This study aiming assessing the immunohistochemical expression of CD44 & OPN in colorectal adenomas & CRCs. And their relation between immunohistochemical expression of CD44 & OPN with tumor differentiation (grading), lympho-vascular invasion, perineural invasion, desmoplasia and TNM stage. Methods: the study is a retrospective descriptive study that included forty-two paraffin embedded blocks from the pathology laboratory, Suez Canal University Hospital. Paraffin blocks included, paraffin blocks reviewed for clinicopathological prognostic factors and stained by CD44 & OPN, monoclonal antibodies by immunohistochemical method. Results: The CD44 protein was expressed in 80% of CRC, the expression of CD44 and lympho-vascular invasion and tumor stage. Conclusions: CD 44 is highly expressed in large number of CRC (80 of tumors). 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 overexpression with both late TNM stage and lymphovascular invasion.