The effectiveness of prophylactic mastectomy in preventing breast cancer was studied in female albino Sprague-Dawley rats. Group A served as untreated controls. Groups B, C, and D underwent 50%, 75%, and total mastectomies 2 weeks after the administration of 7,12-dimethylbenzanthracene (DMBA). Group E was initially subjected to total mastectomy. Two weeks after surgery, group E received 5 mg of DMBA intravenously. Group F underwent sham procedures. All animals were sacrificed at age 8 months. The mean number of tumors per animal developing in groups A through E was 5.00, 5.17, 4.67, 5.46, and 5.20, respectively. There was 0.21 tumor per animal in group F. The mean time to tumor development in groups A through E was 11.33, 10.05, 9.88, 19.25, and 19.38 weeks, respectively. All results were subjected to an analysis of variance. There was no statistically significant difference in the number of DMBA-induced tumors in groups A through E. Groups D and E had a significant prolonged time to tumor development. The overall risk of the development of breast tumors was not significantly reduced by prophylactic mastectomy. Residual breast tissue after prophylactic mastectomy is at increased risk for the development of breast tumors. The risk of developing breast tumors in this model is not reduced in proportion to the amount of breast tissue removed. (This study suggests that subcutaneous mastectomy in high-risk individuals may not have appropriate prophylaxis against the development of carcinoma of the breast.)