Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and more than 90% of neoplasms arising from the kidney. Uninformative percutaneous kidney biopsies vary from 10 to 23%. As a result, 7.5-33.6% of partial nephrectomies in patients with small renal masses (SRM) are performed on benign renal tumors. The aim of this study was to assess the feasibility of the apparent diffusion coefficient (ADC) of the diffusion-weighted imaging (DWI) of MRI, as RCC imaging biomarker for differentiation of SRM. Adult patients (n = 158) with 170 SRM were enrolled into this study. The control group were healthy volunteers with normal clinical and radiologic findings (n = 15). All participants underwent MRI with DWI sequence included. Mean ADC values of solid RCC (1.65 +/- 0.38 x 10(-3) mm(2)/s) were lower than healthy renal parenchyma (2.47 +/- 0.12 x 10(-3) mm(2)/s, p < 0.05). There was no difference between mean ADC values of ccRCC, pRCC and chRCC (1.82 +/- 0.22 x 10(-3) vs 1.61 +/- 0.07 x 10(-3) vs 1.46 +/- 0.09 x 10(-3) mm(2)/s, respectively, p = ns). An inverse relationship between mean ADC values and Fuhrman grade of nuclear atypia of solid ccRCCs was observed: grade I-1.92 +/- 0.11 x 10(-3) mm(2)/s, grade II-1.84 +/- 0.14 x 10(-3) mm(2)/s, grade III-1.79 +/- 0.10 x 10(-3) mm(2)/s, grade IV-1.72 +/- 0.06 x 10(-3) mm(2)/s. This was significant (p < 0.05) only between tumors of I and IV grades. Significant difference (p < 0.05) between mean ADC values of solid RCCs, benign renal tumors and renal cysts was observed (1.65 +/- 0.38 x 10(-3) vs 2.23 +/- 0.18 x 10(-3) vs 3.15 +/- 0.51 x 10(-3) mm(2)/s, respectively). In addition, there was a significant difference (p < 0.05) in mean ADC values between benign cysts and cystic RCC (3.36 +/- 0.35 x 10(-3) vs 2.83 +/- 0.21 x 10(-3) mm(2)/s, respectively). ADC maps with b values of 0 and 800 s/mm(2) can be used as an imaging biomarker, to differentiate benign SRM from malignant SRM. Using ADC value threshold of 1.75 x 10(-3) mm(2)/s allows to differentiate solid RCC from solid benign kidney tumors with 91% sensitivity and 89% specificity; ADC value threshold of 2.96 x 10(-3) mm(2)/s distinguishes cystic RCC from benign renal cysts with 90% sensitivity and 88% specificity. However, the possibility of differentiation between ccRCC histologic subtypes and grades, utilizing ADC values, is limited.