Although recent years have brought many advantages in clinical oncology, colon cancer is still a serious problem. Surgical resection remains the most efficient treatment, but its results are not always satisfactory. To improve disease-free survival, overall survival, and to prevent metastases, new strategies for effective treatment are searched for. Immunotherapy using monoclonal antibodies was shown to be effective in some types of malignancies, however one of the most important obstacles to this type of treatment is attributed to the presence of the complement inhibitors on cancer cells. The three main membrane-bound complement inhibitors that limit the efficacy of the complement-mediated cytotoxicity on cancer cells are CD46, CD55 and CD59. In the current study, we evaluated the expression of these three complement inhibitors on colon cancer tumor samples. Additionally we compared, in samples obtained from the same patients, the immunoreactivities of these inhibitors in the primary and metastatic sites of the tumor. We found that in colon cancer cells the most common is CD46, whereas CD55 and CD59 are present in a small percentage of tumor samples. Although the staining intensity varied between primary and metastatic foci, these results, regarding all examined complement inhibitors were not statistically relevant. It appears that CD46 plays the most significant role among complement inhibitors in colon cancer. Thus, attempts should be made to inhibit this regulator when complement-mediated cytotoxicity is taken into consideration as an option for control of cancer cells remaining after surgical resection of the tumor.