Several recent epidemiologic and experimental studies have suggested that decreased calcium and vitamin D intake and high dietary fat are associated with mammary gland carcinogenesis. Complete reduction or elimination of human exposure to environmental factors such as high-fat diets is inherently difficult to implement. Recent studies have begun to evaluate a possible role for increased dietary calcium and vitamin D in reducing the risk of colonic and mammary cancers, even in the presence of a high-fat diet. Studies from our laboratory recently found that decreased dietary calcium and vitamin D in a high-fat diet induced adverse changes in the mammary gland and several other organs, which were reversed by increasing dietary calcium and vitamin D; the findings further suggest a possible role for increased dietary calcium and vitamin D in the chemoprevention of these cancers.