Formation of mutagenic heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) is one pathway believed to drive the association of colon cancer with meat consumption. Limited data exist on the associations of individual HCAs and PAHs in red or white meat with colon cancer. Analyzing data from a validated meat preparation questionnaire completed by 1062 incident colon cancer cases and 1645 population controls from an ongoing case-control study, risks of colon cancer were estimated using unconditional logistic regression models, comparing the fourth to the first quartile of mutagen estimates derived from a CHARRED based food frequency questionnaire. Total dietary intake of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) [adjusted odds ratio (aOR) = 1.87, 95% confidence interval (CI) = 1.44-2.44, P(trend) < 0.0001], 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) (aOR = 1.68, 95% CI = 1.29-2.17, P(trend) = 0.001) and meat-derived mutagenic activity (aOR = 1.77, 95% CI = 1.36-2.30, P(trend) < 0.0001) were statistically significantly associated with colon cancer risk. Meat type specific analyses revealed statistically significant associations for red meat-derived MeIQx, DiMeIQx, and mutagenic activity but not for the same mutagens derived from white meat. Our study adds evidence supporting red meat-derived, but not white-meat derived HCAs and PAHs, as an important pathway for environmental colon cancer carcinogenesis.