Objective To investigate the conventional and contrast-enhanced ultrasonographic features of clear cell renal cell carcinoma (ccRCC) and renal angiomyolipoma (RAML), and to explore the application value of the 2 methods in the differential diagnosis of ccRCC and RAML. Methods The conventional and contrast-enhanced ultrasound images of 88 foci in 86 ccRCC patients and 38 foci in 31 RAML patients who were diagnosed by pathology, enhanced computed tomography (CT), magnetic resonance imaging (MRI) examination or follow-up were analyzed retrospectively. The size, echo, boundary and vascular architecture of the tumor were observed by conventional ultrasound, the indexes including the modes of perfusion and clearance, intensity and uniformity of perfusion, and peripheral ring enhancement were observed by contrast-enhanced ultrasound, and the value of ultrasonographic features of the conventional and contrast-enhanced ultrasounds in the differential diagnosis of ccRCC and RAML was analyzed. Results There were significant differences in the echo level, blood supply distribution, perfusion modes, perfusion intensity, uniformity and peripheral ring enhancement between ccRCC and RAML (all P<0.05). ccRCC was dominated by hypoechoic (78.41%, 69/88), rich blood supply (53.41%, 47/88), rapid wash-in (95.45%, 84/88), hyperperfusion (93.18%, 82/88) and heterogeneous perfusion (71.59%, 63/88), and peripheral ring enhancement was more common (34.09%, 30/88) in ccRCC; while RAML was dominated by non-hypoechogenicity (86.84%, 33/38), poor blood supply (68.42%, 26/38), hypoperfusion (65.79%, 25/38) and homogeneous perfusion (84.21%, 32/38), rapid or slow wash-in each accounted for 50.00% (19/38), and peripheral ring enhancement was rare (10.53%, 4/38). The accuracy and sensitivity of conventional ultrasound combined with contrast-enhanced ultrasound in the differential diagnosis of ccRCC and RAML in the hypoechoic group were better than those of conventional ultrasound (accuracy 89.19% vs 59.46%, sensitivity 89.86% vs 57.97%; both P<0.01); the accuracy, sensitivity and negative predictive value for the differential diagnosis of ccRCC and RAML in the non-hypoechoic group were better than those of conventional ultrasound (accuracy 78.85% vs 55.77%, sensitivity 84.21% vs 36.84%, negative predictive value 89.29% vs 64.71%; all P<0.05). Conclusion Conventional ultrasound combined with contrast-enhanced ultrasound has high clinical value in the differential diagnosis of ccRCC and RAML; some atypical foci, however, need to be diagnosed comprehensively by combining other examinations.