To compare the diagnostic performance of different mathematical models for DWI and explore whether parameters reflecting spatial and temporal heterogeneity can demonstrate better diagnostic accuracy than the diffusion coefficient parameter in distinguishing benign and malignant breast lesions, using whole-tumor histogram analysis.This retrospective study was approved by the institutional ethics committee and included 104 malignant and 42 benign cases. All patients underwent breast magnetic resonance imaging (MRI) with a 3.0 T MR scanner using the simultaneous multi-slice (SMS) readout-segment ed echo-planar imaging (rs-EPI). Histogram metrics of Mono- apparent diffusion coefficient (ADC), CTRW, and FROC-derived parameters were compared between benign and malignant breast lesions, and the diagnostic performance of each diffusion parameter was evaluated. Statistical analysis was performed using Mann-Whitney U test and receiver operating characteristic (ROC) curve.The DFROC-median exhibited the highest AUC for distinguishing benign and malignant breast lesions (AUC = 0.965). The temporal heterogeneity parameter αCTRW-median generated a statistically higher AUC compared to the spatial heterogeneity parameter βCTRW-median (AUC = 0.850 and 0.741, respectively; p = 0.047). Finally, the combination of median values of CTRW parameters displayed a slightly higher AUC than that of FROC parameters, with no significant difference however (AUC = 0.971 and 0.965, respectively; p = 0.172).The diffusion coefficient parameter exhibited superior diagnostic performance in distinguishing breast lesions when compared to the temporal and spatial heterogeneity parameters.Copyright © 2024 Elsevier Inc. All rights reserved.