A high level of available tissue iron may increase the risk of cancer through its contribution to the production of free oxygen radicals. Serum iron, total iron-binding capacity (TIBC) and transferrin saturation levels were studied for their prediction of different cancers in a cohort of 41,276 men and women aged 20-74 years and initially free from cancer. During a mean follow-up of 14 years, 2,469 primary cancer cases were diagnosed. Excess risks of colorectal and lung cancers were found in subjects with transferrin saturation level exceeding 60%. The relative risks, adjusted for age, sex and smoking, were 3.04 for colorectal cancer and 1.51 for lung cancer, in comparison with subjects having lower levels. The risk of lung cancer was inversely related to serum TIBC, with a relative risk between the highest and lowest quartiles of 0.69 for men and 0.19 for women. For the risk of stomach cancer, we detected inverse relationships with serum iron and with transferrin saturation and a positive relationship with TIBC, but these associations weakened when the cancer cases occurring during the 5 first years of follow-up were excluded. High iron stores may increase the risk of colorectal cancer, whereas low iron stores may be an early sign of occult stomach cancer.