To compare the diagnostic performance of mono-exponential model-derived apparent diffusion coefficient (ADC), continuous-time random-walk (CTRW) model-derived Dm, α, β and their combinations in discriminating malignancy of breast lesions, and investigate the association between model-derived parameters and prognosis-related immunohistochemical indices.A total of 85 patients with breast lesions (51 malignant, 34 benign) were analysed in this retrospective study. Clinical characteristics include oestrogen receptor (ER), progesterone receptor (PR), human epidermal receptor 2 (HER2), and Ki-67. The ADC was fitted using a mono-exponential model (b-values = 0, 800 s/mm2), while Dm, α, and β were fitted using a CTRW model. Independent Student's t-test and the Mann-Whitney U-test were used for the comparison of parameters. Discrimination performance was accomplished by receiver operating characteristic (ROC) analysis, and Spearman's correlation analysis was used to explore the association between immunohistochemical indices and diffusion parameters, the statistical significance level was p<0.05.Dm and ADC demonstrated similar performance in differentiating malignant and benign lesions (AUC = 0.928 versus 0.930), while the combination of Dm, α, and β could improve the AUC to 0.969. The combined parameter generated by ADC, Dm, α, and β was effective in identifying the ER+/ER- and PR+/PR- patients. Temporal heterogeneity parameter α correlated significantly with the expression of PR.Diffusion parameters derived from the CTRW model could effectively discriminate the malignancy of breast lesions. Meanwhile, the hormone receptor expression could be distinguished by combined diffusion parameters, and have the potential to reflect the prognosis.Copyright © 2023. Published by Elsevier Ltd.