The relation between asbestos exposure and colorectal cancer remains controversial. The authors of this 1984-2004 US study examined the association among 3,897 occupationally exposed participants in the Beta-Carotene and Retinol Efficacy Trial (CARET) for chemoprevention of lung cancer, followed prospectively for 10-18 years. When a Cox stratified proportional hazards model was used, risks of colorectal cancer were elevated among male heavy smokers exposed to asbestos. Their relative risk was 1.36 (95% confidence interval: 0.96, 1.93) when compared with that for CARET heavy smokers not exposed to asbestos, after adjusting for age, smoking history, and intervention arm. The presence of asbestos-induced pleural plaques at baseline was associated with a relative risk of 1.54 (95% confidence interval: 0.99, 2.40); colorectal cancer risk also increased with worsening pulmonary asbestosis (p = 0.03 for trend). A dose-response trend based on years of asbestos exposure was less evident. Nonetheless, these data suggest that colorectal cancer risk is elevated among men occupationally exposed to asbestos, especially those with evidence of nonmalignant asbestos-associated radiographic changes.