The aim of this study was to separate the effects of calorie intake on tumorigenesis from those of fat content and fat composition in an animal model. Our principal observations were the following. Decreasing the calorie level by 30% significantly inhibited tumor development in any observed parameter of tumorigenesis, independently of the level of fat. The fat content of semi-synthetic diets, although varying by 44.4%, did not significantly influence mammary tumorigenesis; in fact, carcinogenic expression was discontinuously related to the fat level. A plateau of tumor incidence was observed at the level of 35 energy percentage of fat. Fat composition did not influence tumorigenesis or body weight gain. The role of caloric restriction is thus stressed in relation to possible dietary prevention of cancer.