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The epidemiologic literature in the English language regarding intake of tomatoes and tomato-based products and blood lycopene (a compound derived predominantly from tomatoes) level in relation to the risk of various cancers was reviewed. Among 72 studies identified, 57 reported inverse associations between tomato intake or blood lycopene level and the risk of cancer at a defined anatomic site; 35 of these inverse associations were statistically significant. No study indicated that higher tomato consumption or blood lycopene level statistically significantly increased the risk of cancer at any of the investigated sites. About half of the relative risks for comparisons of high with low intakes or levels for tomatoes or lycopene were approximately 0.6 or lower. The evidence for a benefit was strongest for cancers of the prostate, lung, and stomach. Data were also suggestive of a benefit for cancers of the pancreas, colon and rectum, esophagus, oral cavity, breast, and cervix. Because the data are from observational studies, a cause-effect relationship cannot be established definitively. However, the consistency of the results across numerous studies in diverse populations, for case-control and prospective studies, and for dietary-based and blood-based investigations argues against bias or confounding as the explanation for these findings. Lycopene may account for or contribute to these benefits, but this possibility is not yet proven and requires further study. Numerous other potentially beneficial compounds are present in tomatoes, and, conceivably, complex interactions among multiple components may contribute to the anticancer properties of tomatoes. The consistently lower risk of cancer for a variety of anatomic sites that is associated with higher consumption of tomatoes and tomato-based products adds further support for current dietary recommendations to increase fruit and vegetable consumption.