Intestinal exposure to ingested iron may be a principal determinant of human colorectal cancer risk. Evidence exists associating iron with both the initiating and promoting phases of carcinogenesis as well as somatic defenses against early cancers through hypoferremia (progression or proliferation). Iron intake and the ingestion of associated foods that greatly affect iron bioavailability and absorption (phytate, tannin, ascorbate, and alcohol) vary widely between high-risk and low-risk countries as well as within the United States. These variances in intake may explain not only the gradients in risk between populations, but the crossover in risk between sexes related to age within the United States. Human and rodent studies support the above hypothesis and are reviewed herein, however they are few in number and in many cases lack key data.