Membrane-bound complement regulatory proteins protect cells from the complement-based destruction and affects many vital immunological functions. As was shown by many studies, overexpression of these proteins on cancer cells may have a negative influence on the therapeutic effect of monoclonal antibodies and immunotherapy. The most commonly observed complement inhibitors on cancer cells are CD46, CD55 and CD59. In the presented work we evaluated the expression and immunoreactivity pattern of these three regulators in two colon cancer cell lines, one derived from the primary tumor (SW480), and the other from the lymph node metastasis (SW620). Both cell lines were derived from the same patient. We found that in the SW480 cells the expression of all inhibitors was heterogeneous, within this cell line many subpopulations of cells existed, which displayed different levels of complement inhibitors. On the contrary, on SW620 cells the immunoreactivity of examined inhibitors was more homogeneous, virtually all examined cells displayed complement inhibitors immunoreactivity on the same level. The most prominent in both cell lines was the CD46 expression on the cell surface. Our results indicate that during carcinogenesis progression only these cancer cells may spread, migrate and form metastatic foci, which possess more complement inhibitors on their cell surface. Modulation of the function of membrane-bound complement inhibitors may have beneficial influence on such strategies as immunotherapy with monoclonal antibodies.