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Objective To evaluate the value of parameters derived from intravoxel incoherent motion diffusion-weighted magnetic resonance imaging in differentiating histopathological subtypes of renal cell carcinoma (RCC). Methods Between May 2014 and December 2015, a total of 69 patients who were surgically and pathologically diagnosed as renal cell carcinoma were recruited for the study. We examined 61 clear cell RCC (ccRCC), and 8 non-clear cell carcinoma (non-ccRCC, including 7 chromophobe RCC and 1 papillary RCC). All the ccRCC were divided into well differentiated group (n=46), moderately differentiated group (n=8), and poorly differentiated group (n=7). In addition to routine renal magnetic resonance imaging examination performed on a 3.0-Tesla MR system, all patients were imaged with axial intravoxel incoherent motion diffusion-weighted imaging. Using biexponential model, we calculated the diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f). Results The D and f values of the ccRCC were higher (each P<0.05) than that for non-ccRCC [D (1.29±0.30)×10-3mm2/s, D* (42.92±20.21)×10-3mm2/s, and f (35.71±6.61)% versus D (0.78±0.23)×10-3mm2/s, D* (32.60±11.33)×10-3mm2/s, and f (21.52±8.44)% ]. In the well differentiated group of ccRCC, we found D of (1.36±0.29)×10-3mm2/s, D* (38.39±18.51)×10-3mm2/s, and f (36.40±6.96)%. The D, D*, f values of moderately differentiated lesions were (1.10±0.24)×10-3mm2/s, (59.90±20.23)×10-3 mm2/s, and (32.88±4.02)%, respectively, those of the poorly differentiated group were (1.03±0.16)×10-3mm2/s, (53.28±18.74)×10-3mm2/s, and (34.42±6.21)%. The well differentiated group of ccRCC showed a higher D value than the moderately differentiated and poorly differentiated groups (each P<0.05). D* values were significantly lower for the well differentiated group than for the moderately differentiated group (P<0.05). The sensitivity and specificity of D values were 90.2% and 87.5% when focusing on the differentiation of ccRCC. For the diagnosis of ccRCC, the sensitivity and specificity of f values were 98.4% and 75.0%, respectively. Conclusions IVIM-DWI can provide certain reliable value in evaluating pathological subtype and differentiation degree of renal cell carcinomas. D and f values are useful to distinguish ccRCC from non-ccRCC. D value is also promising for estimating the differentiation degree of ccRCC, and to indicate the biological behavior of RCC. [ABSTRACT FROM AUTHOR]