As the use of depot medroxyprogesterone acetate (DMPA) contraception increases in the United States and worldwide, assessing any impact on the risk of breast and gynecologic cancers becomes increasingly important. Overall, use of DMPA does not affect breast cancer risk. An elevated risk of this disease, however, has been noted in recent or current users. Hence, the association between DMPA use and breast cancer risk appears similar to that observed with oral contraceptives. Use of DMPA is associated with an 80% risk reduction of endometrial adenocarcinoma, a level of protection even greater than that noted with oral contraceptives. The risk of epithelial ovarian cancer and cervical neoplasia does not appear to be affected by DMPA use. Except for a substantial reduction in the risk of endometrial adenocarcinoma, use of DMPA does not appear to influence reproductive tract cancer risks.