Ecological, case-control, and cohort studies present convincing evidence that diets rich in fresh fruit and vegetables protect against several common epithelial neoplasms. Studies of the Mediterranean diet are of particular interest to better understand and quantify this effect in view of the frequency and range of fruit and vegetable consumption by these populations. We review the results of a large-scale, Italian, case-control study of dietary intake of fruit and vegetables and risk of cancer at several sites. The relative risks (RRs) for most common neoplasms ranged from 0.2 to 0.5 for the highest compared with the lowest tertile of vegetable intake. Protective effects of vegetables were also observed against hormone-related neoplasms. Higher intakes of fruit were related to a reduced RR for cancers of the oral cavity and pharynx, esophagus, stomach, or larynx, as well as of the urinary tract, although protection was less evident for other digestive tract sites, as well as for other epithelial cancers. No association was observed between fruit and vegetable consumption and nonepithelial neoplasms. For upper respiratory and digestive tract cancers, population attributable risks for fresh vegetable and fruit intake ranged from 18% to 40% in men and from 15% to 30% in women; attributable risks for fresh vegetable and fruit intake, combined with tobacco and alcohol, exceeded 85% for men and 55% for women.