In order to study the relationship between tomatoes, tomato products, lycopene and cancers of the upper aerodigestive tract (UADC; oral cavity, pharynx, larynx, esophagus) a case-control study was carried out in Uruguay, in the time period 1996-98. Two-hundred and thirty eight cases and 491 hospitalized controls were frequency matched on age, sex, residence and urban/rural status. Both series were submitted to a detailed questionnaire, including tobacco smoking, alcohol drinking and queries on 64 food items. These data were analyzed by unconditional logistic regression, after adjusting by total energy intake. Tomato intake was associated with a reduction in risk of 0.30 (95% confidence interval [CI], 0.18-0.51), whereas tomato sauce-rich foods displayed a protective effect of 0.57 (95% CI, 0.33-0.96 for the highest quartile of intake). The food group composed of raw tomato and tomato-rich foods showed a strong inverse association with UADC (odds ratio [OR], 0.23; 95% CI, 0.13-0.39 for the highest quartile of intake). Lycopene was also strongly associated with a reduced risk of 0.22 (95% CI, 0.13-0.37). Adjustment of tomato intake for several phytochemicals explained almost completely its protective effect, which disappears in this model. Finally, the joint effect of lycopene and total phytosterols was associated with a significant reduction in risk (OR, 0.11; 95% CI, 0.05-0.23).