The growing incidence of colorectal cancer (CRC) in the world seems to be related to the spread of Westernized lifestyles, particularly dietary habits. Several studies have found that high consumption of red meat-especially processed red meat, a mainstay of Western diets-is associated with an increased risk of developing CRC. One possible reason for the association are the adverse effects exerted by the heme iron contained in red meat, which has the potential to affect homeostasis and colonic epithelial cell renewal and to promote the formation of mutagenic and carcinogenic agents. A correlation has also emerged between CRC and alterations of the gut microbiota, since the micro-organisms found in the intestinal lumen seem to influence the activation of enterocyte genes involved in the initiation and progression of carcinogenesis. Dietary habits can therefore modify the gut microbiota, affecting gene activation and favoring the development of cancer cells. We review and discuss the most recent literature on the hypothesis that heme iron can exert adverse effects by altering the gut microbiota and colorectal epithelial cell homeostasis.