Purpose: Although diffusion-weighted imaging(DWI)has emerged as an important method for breast cancer detection and evaluation,there still lacks standardization of quantitative apparent diffusion coefficient(ADC)metrics to describe the wholelesion heterogeneity.This study was performed to establish the ADC as a robust biomarker for estimating the probability of malignancy in breast masses Methods: We retrospectively included 101 women with breast mass lesions(benign: malignant=36: 65)who underwent DWI and subsequently had their histopathologic confirmation.ADC histogram parameters were derived for the whole lesion volume in each patient.Results: The Mann–Whitney U test showed that the mean,minimum,maximum,10th/25th/50th/75th/90th percentile ADCs were significantly lower(all P<0.0001),while the skewness and entropy ADCs were significantly higher(P<0.001 and P =0.001,respectively)in malignant lesions compared with benign ones.The areas under the receiver-operating characteristic curve(Az)of the minimum and 25th percentile ADCs were significantly higher than that of the mean ADC(P =0.0247 and P =0.0206,respectively),indicating that the minimum and 25th percentile ADCs may be more accurate for lesion discrimination.Additionally,the minimum and 25th percentile ADCs had excellent interobserver agreement.Conclusion: These results suggest that the whole-lesion ADC histogram analysis may facilitate the differentiation between benign and malignant breast mass lesions.