【Purpose】To explore the value of ultrasomics in differential diagnosis of benign and malignant breast lesions of BI-RADS category 4.【Methods】A total of 223 patients with BI-RADS category 4 breast lesions with pathology results were reviewed prospectively from June 2018 to December 2019. The study population was divided into the training group (n=114) and validation group (n=109). The ultrasomics score of breast lesion was developped based on the training group. Receiver operating characteristic (ROC) curve of the ultrasomics score was plotted. Area under the curve (AUC) was calculated to quantitatively assess the differential diagnostic performance of ultrasomics score. The sensitivity and specificity were calculated and verified in the validation group.【Results】Among the 223 lesions included, malignancy accounted for 32.29%. The malignant proportions in the training and validation groups were 28.95% and 35.78%, respectively. The AUC with 95% confidence interval of the ultrasomics score in the training and validation groups were 0.826 (0.743-0.909) and 0.810 (0.723-0.898), respectively. In the training group, the sensitivity and specificity of ultrasomics scores to distinguish benign and malignant BI-RADS category 4 lesions were 78.79% and 81.48%, respectively. In the validation group, the corresponding sensitivity and specificity were 66.67% and 82.86%, respectively.【Conclusion】The ultrasomics score has good differential diagnosis value in breast lesions of BI-RADS category 4.