Background: We aimed to assess whether clear cell renal cell carcinoma (ccRCC) can be differentiated from renal oncocytoma (RO) on a contrast-enhanced ultrasound (CEUS). Methods: Between January 2021 and October 2022, we retrospectively queried and analyzed our prospectively maintained dataset. Renal mass features were scrutinized with conventional ultrasound imaging (CUS) and CEUS. All lesions were confirmed by histopathologic diagnoses after nephron-sparing surgery (NSS). A multivariable analysis was performed to identify the potential predictors of ccRCC. The area under the curve (AUC) was depicted in order to assess the diagnostic accuracy of the multivariable model. Results: A total of 126 renal masses, including 103 (81.7%) ccRCC and 23 (18.3%) RO, matched our inclusion criteria. Among these two groups, we found significant differences in terms of enhancement (homogeneous vs. heterogeneous) (p< 0.001), wash-in (fast vs. synchronous/slow) (p= 0.004), wash-out (fast vs. synchronous/slow) (p= 0.001), and rim-like enhancement (p< 0.001). On the multivariate logistic regression, heterogeneous enhancement (OR: 19.37;p= <0.001) and rim-like enhancement (OR: 3.73;p= 0.049) were independent predictors of ccRCC. Finally, these two variables had an AUC of 82.5% and 75.3%, respectively. Conclusions: Diagnostic imaging for presurgical planning is crucial in the choice of either conservative or radical management. CEUS, with its unique features, revealed its usefulness in differentiating ccRCC from RO.