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Background Colorectal cancer is the third most commonly diagnosed cancer in men and the second in women. b-Catenin plays an important role in the WNT signaling pathway. Mutations in Wnt/adenomatous polyposis coli/b-catenin (CTNNB1) signaling pathway members have been found in many colorectal carcinomas. The human epidermal growth factor receptor 2/neu (HER2/neu) gene is located on the chromosomal region 17q12. It encodes a transmembrane glycoprotein that belongs to the EGF/erbB growth factor receptor family. HER2/neu expression has been reported in colorectal cancer and is one of the most promising targeted therapies in the treatment of this type of malignancy.Aim The aim of this study was to study the significance of b-catenin and HER2/neu expression in colorectal carcinomas in correlation with the histopathological parameters. Materials and methodsThis study included 58 previously diagnosed cases of colonic adenocarcinoma together with the adjacent mucosa of all cases. Immunohistochemical expression of b-catenin and HER2/neu was studied, and correlation of their expression with different histopathologic features was performed.Results A statistically significant relationship was found between b-catenin expression and the tumor grade, the stage, and the lymph node status, whereas the relationship of HER2/neu expression with other parameters was statistically insignificant.Conclusion The evaluation of b-catenin expression combined with other pathologic parameters may yield more accurate information about the prognosis of colonic adenocarcinoma, whereas no such information may be obtained with HER2/neu expression.