PurposeTo evaluate if a computer-aided diagnosis (CAD) system on ultrasound (US) can improve the diagnostic performance of inexperienced radiologists. MethodsWe collected ultrasound images of 256 breast lesions taken between March and May 2020. We asked two experienced and two inexperienced radiologists to retrospectively review the US features of each breast lesion according to the Breast Imaging Reporting and Data System (BI-RADS) categories. A CAD examination with S-Detect™ software (Samsung Healthcare, Seoul, South Korea) was conducted retrospectively by another uninvolved radiologist blinded to the BIRADS values previously attributed to the lesions. Diagnostic performances of experienced and inexperienced radiologists and CAD were compared and the inter-observer agreement among radiologists was calculated. ResultsThe diagnostic performance of the experienced group in terms of sensitivity was significantly higher than CAD (p < 0.001). Conversely, the diagnostic performance of inexperienced group in terms of both sensitivity and specificity was significantly lower than CAD (p < 0.001).We obtained an excellent agreement in the evaluation of the lesions among the two expert radiologists (Kappa coefficient: 88.7%), and among the two non-expert radiologists (Kappa coefficient: 84.9%). ConclusionThe US CAD system is a useful additional tool to improve the diagnostic performance of the inexperienced radiologists, eventually reducing the number of unnecessary biopsies. Moreover, it is a valid second opinion in case of experienced radiologists.