Objective The study aims to investigate the value of automated breast ultrasound system (ABUS) combined with computer-aided detection (CAD) for the diagnosis of malignant breast lesions by different experienced readers. Methods A total of 1452 cases assessed on ABUS were collected. All had either pathology diagnosis or follow-up for 1 years. Compare the diagnosis sensitivity, specificity, area under curve (AUC) and reading time of 6 readers (experienced and inexperienced) before and after using CAD system. Results Of the 1452 cases, 270 were malignant (282 lesions), 674 were benign (695 lesions), and 508 were negative. Before using CAD, the sensitivity of novice readers and experienced readers were 87% and 93%, respectively; which was 94% and 94% respectively after using CAD. Statistic difference (P<0.05) was existed between the novice readers before and after using CAD; whereas no statistic difference was existed in the experienced readers before and after using CAD (P>0.05). Diagnostic specificity in all six readers decreased slightly by the use of CAD, yet there was no statistical significance (P>0.05). Diagnostic accuracy, measured by AUC, for novices without CAD was 0.85, for novices with CAD was 0.89, with significant statistic differences (P<0.05). Although there was improvement of AUC after using CAD in experienced reader (0.91 vs 0.92), but no significant statistic difference was found (P>0.05). Reading time extended for all readers with CAD, the differences were statistically significant (P<0.05). Conclusions Although the reading time after the use of CAD has been extended, but ABUS-CAD can greatly improve the diagnostic accuracy of novice readers, which is significant for young doctors.