A varied diet may have a favorable role against digestive tract cancers. We analyzed the relationship between diet diversity (i.e. measured by the number of different foods consumed at least once per week) and the risk of esophageal cancer. We considered data from a case–control study conducted between 1992 and 1997 in northern Italy on 304 squamous cell esophageal cancer cases below age 78 years and 743 controls admitted to hospital for acute, nonneoplastic conditions, unrelated to tobacco or alcohol consumption. There was a significant inverse association for total diet diversity: the multivariate odds ratio (OR), adjusted for age, sex, area of residence, education, tobacco smoking, alcohol drinking and non-alcohol energy intake was 0.42 (95% confidence interval, CI: 0.25–0.71) for subjects in the highest versus those in the lowest quartile of diversity. Inverse relations were also found for diversity within vegetables (OR = 0.34, 95% CI: 0.21–0.55) and fruits (OR = 0.51, 95% CI: 0.33–0.80). No significant association was found for meat and cereal diversity. These results add epidemiological support to the dietary guidelines recommending a more varied diet, particularly in fruit and vegetables, for esophageal cancer prevention. © 2008 Wiley-Liss, Inc.