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BACKGROUND Lesions of breast imaging reporting and data system (BI-RADS) 4 at mammography vary from benign to malignant, leading to difficulties for clinicians to distinguish between them. The specificity of magnetic resonance imaging (MRI) in detecting breast is relatively low, leading to many false-positive results and high rates of re-examination or biopsy. Diffusion-weighted imaging (DWI), combined with perfusion-weighted imaging (PWI), might help to distinguish between benign and malignant BI-RADS 4 breast lesions at mammography. AIM To evaluate the value of DWI and PWI in diagnosing BI-RADS 4 breast lesions. METHODS This is a retrospective study which included patients who underwent breast MRI between May 2017 and May 2019 in the hospital. The lesions were divided into benign and malignant groups according to the classification of histopathological results. The diagnostic efficacy of DWI and PWI were analyzed respectively and combinedly. The 95 lesions were divided according to histopathological diagnosis, with 46 benign and 49 malignant. The main statistical methods used included the Student t-test, the Mann-Whitney U-test, the chi-square test or Fisher’s exact test. RESULTS The mean apparent diffusion coefficient (ADC) values in the parenchyma and lesion area of the normal mammary gland were 1.82 ± 0.22 × 10-3 mm2/s and 1.24 ± 0.16 × 10-3 mm2/s, respectively (P = 0.021). The mean ADC value of the malignant group was 1.09 ± 0.23 × 10-3 mm2/s, which was lower than that of the benign group (1.42 ± 0.68 × 10-3 mm2/s) (P = 0.016). The volume transfer constant (Ktrans) and rate constant (Kep) values were higher in malignant lesions than in benign ones (all P < 0.001), but there were no significant statistical differences regarding volume fraction (Ve) (P = 0.866). The sensitivity and specificity of PWI combined with DWI (91.7% and 89.3%, respectively) were higher than that of PWI or DWI alone. The accuracy of PWI combined with DWI in predicting pathological results was significantly higher than that predicted by PWI or DWI alone. CONCLUSION DWI, combined with PWI, might possibly distinguish between benign and malignant BI-RADS 4 breast lesions at mammography.