Prediagnostic serum concentrations of dehydroepiandrosterone (DHEA) and its sulfated form (DS) are generally increased in breast cancer patients; serum cortisol concentrations are predictably increased as well. The association of increased adrenal steroids with breast cancer may indicate a causal role. However, administration of DHEA to rats and mice has shown a beneficial effect of DHEA in preventing or suppressing breast cancer in numerous studies. DHEA treatment inhibits the development of spontaneous virally induced mammary cancers and suppresses carcinogen-induced as well as radiation-induced mammary tumors. DHEA also antagonizes the effect of estrogen on growth of human breast cancer xenografts in nude mice. DHEA is effective in suppressing cancer development in other organ systems as well including lung, liver, colon, prostate, lymphatic, and skin cancers. We hypothesize that the increase of DHEA in breast fluid and serum is the result of stress-induced adrenal activation and that the glucocorticoid component is the detrimental component rather than DHEA or DS. The mechanisms by which DHEA suppresses tumor growth includes the non-competitive inhibition of glucose-6-phosphate dehydrogenase, inhibition of cholesterol biosynthesis, immune suppression of virally induced breast cancer, enhancement of natural killer cell cytotoxicity by both DHEA and DS, suppression of IL-6, and promotion of estrogen receptor beta expression. The evidence supports the use of DHEA or its derivatives for suppression of cancers regardless of the mechanism by which the cancer arises.