Objective To explore the diagnostic value of multimodal ultrasound in patients with breast cancer with different expression states of Human Epidermal Growth Factor 2 (HER2) and negative expression of Estrogen Receptor (ER).Methods 136 cases (136 lesions) with ER-negative breast cancer confirmed by pathology were retrospectively analyzed. Including 77 patients with positive HER-2 (groupⅠ) and 59 patients with negative HER-2 (group Ⅱ). Preoperative high frequency gray-scale ultrasound， CDFI， SWE assessments were performed to obtain the corresponding variables. Logistic regression model was established based on the variables with differences above. The ROC curve was drawn and analyzed according to the regression model.Results High frequency gray-scale ultrasound: the maximum diameter of the lesion， microcalcification， the "burr" like change of tumor margin and the hyperechoic halo were different among different expression states of HER2 (all P<0.05). CDFI: there were differences in the blood flow distribution and blood flow resistance index among different expression states of HER2 (all P<0.05). SWE: Young′s modulus of the lesion was different among different HER2 expression states (all P<0.05). Logistic regression showed that microcalcification， margin， RI， Emax and Emean were all independent factors affecting the results of immunohistochemistry. The diagnostic efficiency of Emax index was the best (AUC=0.903)， followed by Emean value (AUC=0.807).Conclusion In breast cancer patients with negative ER expression， the ultrasound multimodality features in different HER2 expression status have certain predictive value for immunohistotyping.