Background: The evidence for red meat as a determinant of colorectal cancer remains equivocal, which might be explained by differences in heme content. Heme is the prooxidant, iron-containing porphyrin pigment of meat and its content depends on the type of meat. Chlorophyll from green vegetables might modify this association. Methods: The Netherlands Cohort Study was initiated in 1986 when a self-administered questionnaire on risk factors for cancer was completed by 120,852 subjects ages 55 to 69 years. After 9.3 years of follow-up through the Cancer Registry, 1,535 incident colorectal cancer cases (869 men and 666 women) were available. Nineteen of the 150 items in the validated dietary questionnaire related to consumption of specific types of fresh and processed meat. Heme iron content was calculated as a type-specific percentage of the total iron content and chlorophyll content of vegetables was derived from the literature. Results: Multivariate rate ratios for quintiles of heme iron intake and colon cancer were 1.00, 0.98, 1.04, 1.13, and 1.29 (Ptrend = 0.10) among men and 1.00, 1.31, 1.44, 1.18, and 1.20 (Ptrend = 0.56) among women, respectively. No consistent associations were observed for rectal cancer. Rate ratios for colon cancer increased across successive quintiles of the ratio of heme/chlorophyll among men only (1.00, 1.08, 1.01, 1.32, and 1.43; Ptrend = 0.01). No associations were observed between fresh meat and colorectal cancer. Conclusion: Our data suggest an elevated risk of colon cancer in men with increasing intake of heme iron and decreasing intake of chlorophyll. Further research is needed to confirm these results. Copyright © 2006 American Association for Cancer Research.