PurposeThe purpose of this study was to optimize intra‐voxel incoherent motion (IVIM) measurement in diffusion‐weighted imaging (DWI) of breast cancer by separating perfusion and diffusion effects through the determination of an optimal threshold b‐value, thus benign and cancerous breast tissues can be accurately differentiated using IVIM‐derived diffusion and perfusion parameters.Materials and MethodsTwenty‐eight patients, with biopsy‐confirmed breast cancers, were studied with a 3T MRI scanner, using T1‐weighted dynamic contrast‐enhanced MRI images, and diffusion‐weighted images with nine b‐values, ranging from 0 to 1000 s/mm². IVIM‐derived parameter maps for tissue diffusion coefficients D, perfusion fraction f, and pseudo‐diffusion coefficients D* were computed using the segmented fitting method with optimized threshold b‐value, and the sum of squared residuals (SSR) were calculated for IVIM‐derived parameters in different breast lesions.ResultsThe IVIM analysis method developed in this work can separate perfusion and diffusion effects with the optimal threshold b‐value of 300 s/mm², and the results of diffusion and perfusion parameters from IVIM analysis can be used to differentiate pathological changes in breast tissues. It was found that the averages and standard deviations of the diffusion and perfusion parameters, D, f, D*, are the following, for malignant, benign and normal breast tissues respectively: D (0.813 ± 0.225 × 10−3 mm2/s, 1.437 ± 0.538 × 10−3 mm2/s, 1.838 ± 0.213 × 10−3 mm2/s), f (10.73 ± 3.44%, 7.86 ± 3.70%, 8.92 ± 3.72%), D* (15.23 ± 12.17×10−3 mm²/s, 12.02 ± 3.19 × 10−3 mm2/s, 12.03 ± 7.21 × 10−3 mm2/s).Conclusion IVIM‐derived diffusion and perfusion parameter maps depend highly on the choice of threshold b‐value. Using the methodology developed in this work, and with the optimized threshold b‐value, the diffusion and perfusion parameters of breast tissues can be accurately assessed, making IVIM MRI a technique of choice for differential diagnosis of breast cancer.