Mammography is the current standard for breast cancer screening. This study aimed to develop an artificial intelligence (AI) algorithm for diagnosis of breast cancer in mammography, and explore whether it could benefit radiologists by improving accuracy of diagnosis. In this retrospective study, an AI algorithm was developed and validated with 170 230 mammography examinations collected from five institutions in South Korea, the USA, and the UK, including 36 468 cancer positive confirmed by biopsy, 59 544 benign confirmed by biopsy (8827 mammograms) or follow-up imaging (50 717 mammograms), and 74 218 normal. For the multicentre, observer-blinded, reader study, 320 mammograms (160 cancer positive, 64 benign, 96 normal) were independently obtained from two institutions. 14 radiologists participated as readers and assessed each mammogram in terms of likelihood of malignancy (LOM), location of malignancy, and necessity to recall the patient, first without and then with assistance of the AI algorithm. The performance of AI and radiologists was evaluated in terms of LOM-based area under the receiver operating characteristic curve (AUROC) and recall-based sensitivity and specificity. The AI standalone performance was AUROC 0·959 (95% CI 0·952–0·966) overall, and 0·970 (0·963–0·978) in the South Korea dataset, 0·953 (0·938–0·968) in the USA dataset, and 0·938 (0·918–0·958) in the UK dataset. In the reader study, the performance level of AI was 0·940 (0·915–0·965), significantly higher than that of the radiologists without AI assistance (0·810, 95% CI 0·770–0·850; p<0·0001). With the assistance of AI, radiologists' performance was improved to 0·881 (0·850–0·911; p<0·0001). AI was more sensitive to detect cancers with mass (53 90% vs 46 78% of 59 cancers detected; p=0·044) or distortion or asymmetry (18 90% vs ten 50% of 20 cancers detected; p=0·023) than radiologists. AI was better in detection of T1 cancers (73 91% vs 59 74% of 80; p=0·0039) or node-negative cancers (104 87% vs 88 74% of 119; p=0·0025) than radiologists. The AI algorithm developed with large-scale mammography data showed better diagnostic performance in breast cancer detection compared with radiologists. The significant improvement in radiologists' performance when aided by AI supports application of AI to mammograms as a diagnostic support tool. Lunit.