The incidence of certain cancers in the Mediterranean area is lower than in other areas of the world (e.g. in northern Europe and the USA). As nutrition and dietary factors comprise one of the three major factors for human carcinogenesis, the hypothesis was formulated that the dietary profile of the Mediterranean diet, rich in antioxidants, might exert preventive actions. Alas, the vast majority of experiments to prove this hypothesis have been obtained in vitro, and most of the necessary information on the absorption, distribution and metabolism of oligonutrients is currently lacking. Yet, even though the exact role of antioxidants in the Mediterranean diet is yet to be fully established, data from observational studies are strong enough to reinforce the notion that a diet low in saturated fat and alcohol and rich in plant food and whole grain, such as the traditional Mediterranean diet, is associated with lower risk of cancer and should be actively promoted.