As thyroid and breast cancer have several US findings in common, we applied an artificial intelligence computer-assisted diagnosis (AI-CAD) software originally developed for thyroid nodules to breast lesions on ultrasound (US) and evaluated its diagnostic performance. From January 2017 to December 2017, 1042 breast lesions (mean size 20.2 ± 11.8 mm) of 1001 patients (mean age 45.9 ± 12.9 years) who underwent US-guided core-needle biopsy were included. An AI-CAD software that was previously trained and validated with thyroid nodules using the convolutional neural network was applied to breast nodules. There were 665 benign breast lesions (63.0%) and 391 breast cancers (37.0%). The area under the receiver operating characteristic curve (AUROC) of AI-CAD to differentiate breast lesions was 0.678 (95% confidence interval: 0.649, 0.707). After fine-tuning AI-CAD with 1084 separate breast lesions, the diagnostic performance of AI-CAD markedly improved (AUC 0.841). This was significantly higher than that of radiologists when the cutoff category was BI-RADS 4a (AUC 0.621, P < 0.001), but lower when the cutoff category was BI-RADS 4b (AUC 0.908, P < 0.001). When applied to breast lesions, the diagnostic performance of an AI-CAD software that had been developed for differentiating malignant and benign thyroid nodules was not bad. However, an organ-specific approach guarantees better diagnostic performance despite the similar US features of thyroid and breast malignancies.