The current work investigated the possible association between colorectal carcinoma and Helicobacter pylori cytotoxin-associated gene A product (CagA) in Iraqi patients. In an endeavor to understand its possible role in colorectal carcinogenesis, the expression of c-Myc and mucin-2 (MUC-2) proteins was also investigated by immunohistochemical analysis. Accordingly, a total of 30 consecutive patients with colorectal carcinoma were studied (17 men and 13 women) with a mean age of 56.2 years (range between 21 and 82 years). Each patient was interviewed and his/her paraffin-embedded blocks were retrieved. In addition, serum sample was taken preoperatively from each patient. Histopathological data including site, histological type, stage, and grade of the tumor were also obtained. In addition. serum samples were obtained from 30 apparently healthy controls (17 men and 13 women) with a mean age of 52.57 years (range between 21 and 76 years). Sera were examined for the presence of H. pylori CagA immunoglobulin G (IgG) antibodies and carbohydrate antigen 19-9 (CA19-9) by enzyme linked immunosorbent assay (ELISA). The paraffin-embedded sections were investigated for the expression of c-Myc and MUC-2 proteins by immunohistochemistry using specific monoclonal antibodies. Our data analysis demonstrated a significant increase in H. pylori CagA seroprevalence among colorectal cancer patients (p=0.026). The seropositivity rate was 47% and 20% in colorectal cancer patients and controls, respectively. Based on immunohistochemical analysis of the paraffin-embedded sections, the expression of c-Myc and MUC-2 proteins was positively detected in 80% and 63%, respectively. In addition, our results showed that among CagA seropositive patients the positive expression rate was 79% and 40% for c-Myc and MUC-2, respectively; However, no significant difference was found in the expression of both c-Myc and MUC-2 proteins with respect to H. pylori CagA serostatus (p>0.05). According to histopathological data, the current study demonstrated that MUC-2 positive expression was significantly associated with the mucinous type of colorectal carcinoma (p=0.012). In contrast, no significant difference was found between other histopathological parameters and the expression of both c-Myc and MUC-2 p>0.05). CA19-9 was found to be elevated in 53% of colorectal cancer cases. However, no significant difference was found between any of the histopathological parameters and the serum level of CA19-9 (p>0.05). In conclusion, our results confirmed a significant association between colorectal cancer and CagA-positive H. pylori infection. Further larger studies are recommended to shed more insight on its possible role in colorectal carcinogenesis. Although the current study did not show a significant difference between H. pylori CagA seropositivity and expression of c-Myc and MUC-2, however further study based on larger group of patients is recommended in order to validate the findings of the present research.