Neoadjuvant chemotherapy (NAC) reduces tumor size, facilitating the use of breast conservation surgery (BCS). However, mastectomy remains the surgical outcome for certain women. The goal of this study was to determine the rationale for mastectomy after NAC, particularly in women eligible for BCS. Retrospective data were reviewed on patients who received NAC between February 2006 and August 2010 at our institution. Demographics and tumor characteristics were compared between patients who received BCS and mastectomy after NAC. Of 149 patients meeting inclusion criteria, 102 (68%) underwent BCS and 47 (32%) underwent mastectomy. Patient preference was the most common rationale for mastectomy (n = 19; 40%), followed by extent of disease (n = 13; 28%), presence of a breast cancer susceptibility gene (BRCA) mutation (n = 9; 19%), persistent positive margins (n = 5; 11%), and wound complications (n = 1; 2%). Of the 47 patients who underwent mastectomy, 37 (79%) were eligible for BCS after NAC. Larger pathologic tumor size (2.05 vs 1.25 cm, P = 0.04) and lobular histology [invasive lobular carcinomas, n = 12/17 (70%) vs invasive ductal carcinomas, n = 36/133 (27%); P < 0.01] were associated with increased rate of mastectomy. After NAC, patient preference, extent of disease, and the presence of a BRCA mutation account for the vast majority of mastectomies. Interestingly, most of these patients were shown to be candidates for breast conservation. This highlights the importance of educating patients about their surgical choice and the lack of evidence, showing a benefit to more extensive surgery.