European Mediterranean populations have a high life expectancy. Several aspects of their diet are considered favorable on health. We considered the role of various aspects of the Mediterranean diet on cancer risk in a series of Italian case-control studies including about 10,000 cases of cancer at 13 different sites and over 17,000 controls. For most epithelial cancers, the risk decreased with increasing vegetable consumption. Allium vegetables were also favorably related to cancer risk. Fruit intake was inversely associated with digestive tract and laryngeal cancers. For digestive tract cancers, the population attributable risks for low intake of vegetables and fruit ranged between 15% and 40%. Olive oil and unsaturated fats, which are typical aspects of the Mediterranean diet, were inversely related to the risk of several cancers, particularly of the upper aerodigestive tract. Whole grain food (and hence possibly fiber) intake was also related to reduced risk of various cancers. In contrast, refined grains and, consequently, glycemic load and index were associated to increased risks. Several micronutrients and food components (including folate, flavonoids, and carotenoids) showed inverse relations with cancer risk, but the main component(s) responsible for the favorable effect of a diet rich in vegetables and fruit remain undefined.