Over the past several years, increasing evidence suggests that the Mediterranean diet has a beneficial influence on several age-related diseases, showing protective effect on health and longevity. Mediterranean diet refers to dietary patterns found in olive-growing regions of the Mediterranean countries. Previous data reported that in Sicily, Italy, the largest Mediterranean island, there are some mountainous regions where there is a high frequency of male centenarians with respect to the Italian average. The aim of the present study was to characterize centenarians living in one of this region, the Sicani Mountains, located in western Sicily. Present data shows that in this zone there are more centenarians with respect to the Italian average. In fact, in the three villages of the Sicani Mountains, there were 15 people ranging from 100 to 107 years old, of the total population of about 10,000 inhabitants. This centenarian number was more than six-fold higher the national average (15.0 vs. 2.4/10,000); the female/male ratio was 1.5 in the study area, whereas the national ratio is 4.54. Centenarians living in these villages had anthropometric measurements within normal limits and moderate sensory disability without any sign of age-related diseases, including cognitive deterioration and dementia. In addition, their clinical chemistry profile was similar to young controls and far better than that of old controls. Unequivocally, their nutritional assessment showed a high adherence to the Mediterranean nutritional profile, with low glycemic index food consumed. Overall, close adherence to Mediterranean diet seems to play a key role in age-related disease prevention and in attaining longevity.