We evaluated the postoperative course of all patients who had mastectomies from 1978 through 1982 at City of Hope National Medical Center (Duarte, Calif). The overall clean mastectomy wound infection rate was 24/294 (8.2%). The incidence of mastectomy wound infection varied with the method of biopsy and was 3.2% after needle aspiration and 9.5% after open biopsy. Mastectomy immediately after open biopsy ("one step") had an infection rate of 5.3%, whereas mastectomy at a subsequent procedure ("two step") had a rate of 12.4%. The maximal infection rate (23.0%) occurred following the two-step procedure when the interval was four to seven days. The infection rates for patients hospitalized three or more days before mastectomy were elevated, but no significant correlation was observed between the infection rate and other demographic factors. We recommend that needle aspiration biopsy be used prior to open biopsy to minimize the need for a two-step approach to mastectomy.