Many animal and in vitro experiments have shown that the supplementation of diet with vitamin E within a certain dose range reduced the risk of chemical- and radiation-induced cancers. In vitro studies revealed that alpha-tocopheryl succinate (TS) induced differentiation and growth-inhibition in certain animal and human tumor cells in culture, whereas alpha-tocopherol (alpha-T), alpha-tocopheryl acetate (alpha-TA) and alpha-tocopheryl nicotinate (alpha-TN) were ineffective, alpha-TS also reduced basal and ligand-stimulated adenylate cyclase activity, and expression of c-myc and H-ras oncogenes in certain tumor cells in culture. The relative efficacy of various forms of vitamin E in cancer prevention in animal or human models has not been evaluated. Human epidemiologic studies utilizing retrospective and prospective case-control experimental designs are not suitable for evaluating the role of vitamin E in cancer prevention due to several inherent problems associated with these methodologies. Intervention trials utilizing vitamin E with appropriate biological and statistical rationales are most suitable for testing the role of vitamin E in cancer prevention in humans. Some human trials utilizing vitamin E alone or in combination with other nutrients are in progress.