Although fruits and vegetables have been implicated in the etiology of pancreatic cancer, the role of phytochemicals in these food groups has received little attention to date. In this study, we investigated the possible association between dietary carotenoids and pancreatic cancer risk. A case-control study of 462 histologically confirmed pancreatic cancer cases and 4721 population-based controls in 8 Canadian provinces took place between 1994 and 1997. Dietary intake was assessed by a self-administered FFQ. Unconditional logistic regression was used to assess associations between specific and total carotenoid intakes and the risk of pancreatic cancer. All tests of statistical significance were 2-sided. After adjustment for age, province, BMI, smoking, educational attainment, dietary folate, and total energy intake, lycopene, provided mainly by tomatoes, was associated with a 31% reduction in pancreatic cancer risk among men [odds ratio (OR) = 0.69; 95% CI: 0.46-0.96; P = 0.026 for trend] when comparing the highest and lowest quartiles of intake. Both beta-carotene (OR = 0.57; 95% CI: 0.32-0.99; P = 0.016 for trend) and total carotenoids (OR = 0.58; 95% CI: 0.34-1.00; P = 0.02 for trend) were associated with a significantly reduced risk among those who never smoked. The results of this study suggest that a diet rich in tomatoes and tomato-based products with high lycopene content may help reduce pancreatic cancer risk.