Background:The aim of this study was to assess the performance of apparent diffusion coefficient (ADC) measurement obtained with diffusion-weighted magnetic resonance imaging (DW-MRI) to distinguish renal cell carcinomas (RCCs) from small benign solid renal tumors (≤4 cm).Methods:In this cross-sectional study, 49 consecutive patients with histopathologically confirmed small solid renal tumors, and seven healthy volunteers were imaged using nonenhanced MRI and DW-MRI. The ADC map was calculated using the b values of 0, 50, 400, and 600 s/mm2 and values compared via the Kruskal–Wallis and Mann–Whitney tests. The utility of ADC for differentiating RCCs and benign lesions was assessed using a receiver operating characteristic curve. Multiple nonenhanced MRI features were analyzed by Logistic regression.Results:The tumors consisted of 33 cases of clear-cell RCCs (ccRCCs) and 16 cases of benign tumors, including 14 cases of minimal fat angiomyolipomas and 2 cases of oncocytomas. The ADCs showed significant differences among benign tumors ([0.90 ± 0.52] × 10−3 mm2/s), ccRCCs ([1.53 ± 0.31] × 10−3 mm2/s) and the normal renal parenchyma ([2.22 ± 0.12] × 10−3 mm2/s) (P < 0.001). Moreover, there was statistically significant difference between high and low-grade ccRCCs (P = 0.004). Using a cut-off ADC of 1.36 × 10−3 mm2/s, DW-MRI resulted in an area under the curve (AUC), sensitivity, and specificity equal to 0.839, 75.8%, and 87.5%, respectively. Nonenhanced MRI alone and the combination of imaging methods led to an AUC, sensitivity and specificity equal to 0.919, 93.9%, and 81.2%, 0.998, 97%, and 100%, respectively. The Logistic regression showed that the location of the center of the tumor (inside the contour of the kidney) and appearance of stiff blood vessel were significantly helpful for diagnosing ccRCCs.Conclusions:DW-MRI has potential in distinguishing ccRCCs from benign lesions in human small solid renal tumors (≤4 cm), and in increasing the accuracy for diagnosing ccRCCs when combined with nonenhanced MRI.