PurposeTo determine the utility of various diffusion parameters obtained from monoexponential, biexponential, and stretched exponential diffusion-weighted imaging (DWI) models in differentiating between minimal fat angiomyolipoma (MFAML) and clear cell renal cell carcinoma (ccRCC). Materials and MethodsOne hundred thirty-one patients with pathologically confirmed MFAML (n=27) or ccRCC (n=104) underwent multi-b value DWI (0 approximate to 1700 s/mm(2)) imaging at 3.0 Tesla MRI. An isotropic apparent diffusion coefficient (ADC) was calculated from diffusion-weighted images by using a monoexponential model. A pseudo-ADC (D-p), true ADC (D-t), and perfusion fraction (f(p)) were calculated from diffusion-weighted images by using a biexponential model. A water molecular diffusion heterogeneity index () and distributed diffusion coefficient (DDC) were calculated from diffusion-weighted images by using a stretched exponential model. All parameters were compared between MFAML and ccRCC by using the Student's t test. Receiver operating characteristic and intraclass correlation coefficient analysis were used for statistical evaluations. ResultsADC, D-t, and values were significantly lower in the MFAML group than in the ccRCC group (P<0.001). D-p, f(p), and DDC values were slightly higher in the MFAML group than in the ccRCC group; however, the difference was not significant (P=0.136, 0.090, and 0.424, respectively). The AUC values for both (0.953) and D-t (0.964) were significantly higher than those for ADC (0860), D-p (0.605), f(p) (0.596), and DDC (0.477) in the differentiation of MFAML from ccRCC (P<0.001). ConclusionWater molecular diffusion heterogeneity index () and D-t may provide additional information and could lead to improved differentiation with better sensitivity and specificity between MFAML and ccRCC compared with conventional diffusion parameters. Level of Evidence: 3 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:240-247