Both iron-deficient and zinc-sufficient diets have been known to be associated with a decreased risk of colon cancer. We investigated that effect of dietary zinc on the formation of colonic aberrant crypt foci (ACF) induced by azoxymethane (AOM) followed by dextran sodium sulfate in iron-deficient mice. Five-week old ICR mice were acclimated for 1 week and fed on iron-deficient diet (4.50 ppm iron) with three different zinc levels (0.01, 0.1, and 1.0 ppm) for 12 weeks. The total number of aberrant crypt (AC) and ACF was measured in the colonic mucosa after methylene blue staining. The total ACF numbers of low Zn (LZn), medium Zn (MZn) and high Zn (HZn) diet groups were 10.00 ± 2.67, 8.78 ± 3.12, and 7.96 ± 2.44, respectively and there were no significant differences among the groups. However, the total AC numbers of HZn (27.07 ± 3.88) and MZn (26.39 ± 5.59) diet groups were significantly low compared to LZn (22.57 ± 5.09) diet group (p<0.01). Cytosolic SOD activity was the highest in LZn diet group. But thiobarbituric acid-reactive substances level in liver was also the highest in LZn diet group compared to other groups. There is no difference in cell proliferation in mucous membrane among the groups, while apoptotic positive cells were increased in the HZn diet group. The high zinc diet exhibited decreased β-catenin-stained areas on the mucous membrane of colon compared to the LZn or MZn diet group. These findings indicate that dietary zinc might exert a modulating effect on development of ACF/AC in the mice with iron-deficient status.