Objectives-To explore whether conventional elastography and contrast-enhanced ultrasound (CEUS) combined with histopathology can monitor the efficacy of neoadjuvant chemotherapy (NAC) for breast cancer (BC), and develop a Nomogram prediction model monitoring response to NAC. Methods-From February 2010 to November 2015, 91 BC patients who received NAC were recruited. The maximum diameter, stiffness, and CEUS features were assessed. Core biopsy, surgical pathology immunophenotype, and Miller-Payne (MP) evaluation were documented. Univariate and multivariate analysis was performed using receiver operating characteristic (ROC) analysis and logistic regression analysis. Results-There were 37 cases showing pathological complete response (pCR) and 54 of non-pCR. The changes of maximal diameter were correlated with MP (P < .05). The sensitivity (SEN), specificity (SPE), and area under the ROC curve (AUC) of baseline size predicting pCR were 57.40%, 70.30%, and 0.64 (P = .024). Baseline Ki-67 index of pCR group is significantly higher than that of non-pCR group (P = .029), and the ROC analysis of baseline Ki-67 indicates the SEN, SPE, and AUC of 51.70%, 78.00%, and 0.638 (P = .050). When combined with size, CEUS features, stiffness, and Ki-67 of baseline, the ROC curve shows good performance with SEN, SPE, and AUC of 70.00%, 76.19%, 0.821 (P = .004). Incorporating the change of characteristics into multivariate regression analysis, the results demonstrate excellent performance (SEN 100.00%, SPE 95.24%, AUC 0.986, P = .000). Conclusions-The change of the maximum size was correlated with MP score, which can provide reference to predict efficacy of NAC and evaluate residual lesions. When combining with elastography, CEUS, and Ki-67, better performance in predicting pathological response was shown.