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High iron levels can increase the formation of noxious oxygen radicals, which are thought to promote carcinogenesis.The aim of this prospective study was to determine whether iron biomarkers and HFE genotypes, which influence iron regulation, constitute risk factors for colorectal cancer.This is a prospective nested case-referent study.The study was performed within the population-based Northern Sweden Health and Disease Study.The study included 226 cases of colorectal cancer and 437 matched referents.Conditional regression analysis was performed. Adjustments for smoking, smoking and BMI, and HFE C282Y and H63D were performed.The highest quintile of total iron-binding capacity showed significantly higher risk for colorectal cancer, unadjusted OR 2.35 (95% CI 1.38–4.02). When stratified by sex, the findings were only present in women (OR 3.34 (95% CI 1.59–7.02)). Ferritin was associated with reduced risk throughout quintiles 2 to 5 both in univariate and multivariate models.Colorectal cancer may influence iron markers because of occult bleeding. Homozygotes for HFE C282Y were too few to make conclusions for this group. The relatively short follow-up time might be insufficient to detect risk of iron biomarkers.High iron levels do not increase the risk of colorectal cancer. HFE genotypes influencing iron uptake had no effect on colorectal cancer risk.