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Objective: The aim of the study was to explore the protein level of NF-κB change in carcinoma and different grades of tumor cells differentiation tissue in colorectal cancer patients. Methods: This was a comparative study between normal and carcinoma tissues and in different grades of tumor cells differentiation tissue in colorectal cancer patients. Expression of NF-κΒ were assessed by immunohistochemical method using rabbit polyclonal antibodies against human p65 NF-κΒ proteins. Results: There was none or very little expression of NF-κB in non-neoplastic colon epithelial cells, while the expression of its protein was significantly increased (P < 0.01) in adjacent cancerous cells. Moreover, there was a significant increase in the mean expression of NF-κB-p65 between poorly differentiated malignant epithelial cell and well-differentiated cells (P < 0.05). Conclusion: NF-κB-p65 may play an essential role in colorectal carcinogenesis and may be valuable for diagnosis, evaluating malignancy extent and prognosis.