Background The aim of this study was to evaluate factors that could possibly affect the outcome of patients failing to achieve pathological complete response (pCR) after anthracycline‐containing neoadjuvant chemotherapy (NCT) for breast cancer, and built a prognostic model to predict patients' outcome. Patients and Methods Data from 199 stage II–III breast cancer patients who failed to achieve pCR after NCT were used. Variables at baseline and at surgery (age, menopausal status, tumour size, grade, histotype, node status, vascular invasion, ER, PR, HER‐2, Cathepsin D, P53, Topo‐IIα, Nm‐23, Bcl‐2, BAX, MDR, GSTN, PS2, P27, Cyclin D1 and Ki‐67) were investigated. Results Tumour marker Ki‐67, Cathepsin D status and number of positive lymph nodes at surgery were significant prognostic factors in multivariate analysis for both DFS and OS. According to our prognostic model, the 5‐year DFS rates in low, intermediate‐low, intermediate‐high and high‐risk groups were 94%, 65%, 43% and 28%, respectively (log‐rank test P < 0.001). The 5‐year OS rates in these four groups were 94%, 84%, 66% and 34%, respectively (log‐rank test P < 0.001). Conclusion Our prognostic model could easily discriminate patients with different risks of experiencing an event or death, which could allow physicians to tailor treatment strategies specifically and individually. J. Surg. Oncol. 2012; 105:577–585. © 2011 Wiley Periodicals, Inc.