To propose a novel deep learning method incorporating multiple regions based on contrast-enhanced ultrasound and grayscale ultrasound, evaluate its performance in reducing false positives for Breast Imaging Reporting and Data System (BI-RADS) category 4 lesions, and compare its diagnostic performance with that of ultrasound experts.This study enrolled 163 breast lesions in 161 women from November 2018 to March 2021. Contrast-enhanced ultrasound and conventional ultrasound were performed before surgery or biopsy. A novel deep learning model incorporating multiple regions based on contrast-enhanced ultrasound and grayscale ultrasound was proposed for minimizing the number of false-positive biopsies. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy were compared between the deep learning model and ultrasound experts.The AUC, sensitivity, specificity, and accuracy of the deep learning model in BI-RADS category 4 lesions were 0.910, 91.5%, 90.5%, and 90.8%, respectively, compared with those of ultrasound experts were 0.869, 89.4%, 84.5%, and 85.9%, respectively.The novel deep learning model we proposed had a diagnostic accuracy comparable to that of ultrasound experts, showing the potential to be clinically useful in minimizing the number of false-positive biopsies.Copyright © 2023 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.