The objective of the present study was to determine whether neoadjuvant chemotherapy in women with breast cancer larger than 3 cm associated with breast-conserving surgery plus intraoperative evaluation of surgical margins is safe. A total of 164 patients with breast cancer larger than 3 cm in diameter were submitted to neoadjuvant chemotherapy between 1992 and 1998 and followed until 2003. We used neoadjuvant chemotherapy in pulses at 21-day intervals with 5-fluorouracil (500 mg/m2), epirubicin (50 mg/m2) and cyclophosphamide (500 mg/m2) (FEC). Initially, 3 cycles of chemotherapy were administered, followed by surgery and 6 additional chemotherhapy cycles. During surgery, an evaluation of the surgical margins was performed. Quadrantectomy was performed in 102 patients (62.2%) and mastectomy in 62 (37.8%). Local recurrence in 8 patients, metastasis in 37, and 21 deaths were observed. The curves of local recurrence for quadrantectomy and mastectomy were similar (P = 0.654 and P = 0.841, respectively), and so were the numbers of local recurrence (P = 0.4438). The curves of disease-free survival for quadrantectomy and mastectomy were different (P = 0.034 and P = 0.033, respectively). However, no statistically significant difference was observed in the number of events (P = 0.1283). A statistically significant difference was observed for the curves (P = 0.001 and P = 0.000) and the number (P = 0.0034) of deaths between patients undergoing quadrantectomy or mastectomy. Neoadjuvant chemotherapy can reduce surgery complexity and is safe when associated with intraoperative evaluation of the surgical margins, without changing the local recurrence rate, disease-free survival, and overall survival.