In Croatia, colorectal cancer is the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths. Colorectal cancer is a result of multistep process in which malignant colorectal carcinoma develops from benign adenoma, as a result of somatic or inherited mutations. Existing prognostic markers give only partial information about course and outcome of this disease, so there is a constant need for development and discovery of novel disease-related diagnostic and prognostic molecular markers. One of these new markers could be also HER-2. HER-2 is a cell membrane receptor tyrosine kinase, encoded by HER-2/neu gene, and is normally involved in the signal transduction pathways leading to cell growth and proliferation. Previous studies suggested that certain polymorphisms of the HER-2 gene (e.g. I655V) might result in increased autophosphorylation and tyrosine kinase activation. It is possible that these polymorphisms are associated with the increased susceptibility to colon cancer and poor prognosis. The aim of this study was to investigate the potential correlation of polymorphism c.1963A>G (rs1136201, I655V) in HER-2/neu gene with susceptibility to disease and survival of patients suffering from sporadic colorectal cancer. Results showed that I655V polymorphism is related to increased risk for sporadic colon cancer development.