Background and aims:Colorectal carcinoma is among the most frequently observed malignancies in Pakistan. The HER 2/neu protein is intimately involved in tumorigenesis and its receptor has been demonstrated as a therapeutic target in several carcinomas. This study was designed to assess the clinico-pathological pattern and the HER 2/neu immunohistochemical score with respect to the histological grades of colorectal carcinoma in our population. Methods: Tissue biopsies from 100 patients, with detailed documentation of their clinical account, were subjected to immunohistochemistry utilizing monoclonal anti-HER 2/neu antibody. Positive expression was assigned a score from 0-3+. Results: A distinct positive HER 2/neu scoring pattern was observed in n = 42 cases of non-mucinous, mucinous and signet ring cell adenocarcinomas, all with a specific histological grade. An inverse correlation (P = 0.001) was observed between the two parameters. Conclusion: Colorectal carcinoma is a growing malignancy, even in the younger population and HER 2/neu protein is credibly expressed in colonic cancer cells in our patients especially where the histological grade is low or moderate. Therefore, it may be applied as a reasonably reliable immunohistochemical marker and a target for a new adjuvant monoclonal antibody-based immunotherapy.