Background: Neoadjuvant chemotherapy allows direct evaluation of the tumor’s sensitivity to therapy, eradication of micrometastatic disease and the possibility of performing breast conserving surgery. The aim of this study was to describe long-term results of neoadjuvant chemotherapy in stage III breast cancer patients (pts). Methods: We evaluated 126 pts with stage III breast cancer that participated in a phase-II randomized trial of neoadjuvant 5-fluorouracil, doxorubicin and cyclophosphamide (FAC every 21 days) compared with cyclophosphamide, methotrexate and 5-fluorouracil (CMF days 1 and 8 every 28). Chemotherapy was administered for three cycles prior to definitive surgery and radiotherapy, and then for six cycles as adjuvant. Response was assessed by WHO criteria. Results: Pts characteristics were well balanced in both groups (FAC: 64pts, CMF: 62pts). Median follow-up was 4.5 years (range 0.2-16.4). No significant difference was found regarding acute and long-term toxicity; however, alopecia was more frequent in FAC group. Breast conserving surgery was performed in 13.5% of pts with no difference between groups. Objective response rate (OR) was similar in both groups but pathological complete response was achieved by 4 pts who received FAC. Although both groups had similar locoregional and distant recurrences, contralateral breast cancer was higher in the CMF group (6.5% vs 1.6%, P=NS). Disease free survival (DFS) and overall survival (OS) data are shown in the table. After 16 years of follow-up, 42.1% (n=53) of pts are still alive. Disease progression was the principal cause of death in both groups (78.9% vs 84.2%). Conclusions: To the best of our knowledge, this is the first study to report long-term outcomes of FAC and CMF in the neoadjuvant setting. Within the sensitivity of our study, both regimens showed similar OR, long-term toxicity, DFS and OS rate at 16 years. Around 40% of pts are currently alive. Clinical trial information: NCT00002696.