Abstract: Objective To determine the perfusion pattern of lymphadenopathy in contrast-enhanced ultrasonography (CEUS) under different reference conditions. Methods The CEUS perfusion patterns of 78 superficial lymph node lesions were compared with their pathology results. Time-intensity curves were used for comparison between benign and malignant lymph nodes. Results Inhomogeneous hyperenhancement was the main perfusion pattern （7/17, 41.2%） in metastatic lymph nodes; compared with homogeneous hyperenhancement （2/4,50.0%） in lymphoma, homogeneous hyperenhancement and isoenhancement （6/52,11.5%） in reactive lymph nodes, and circle enhancement （2/4,50.0%） in tuberculosis. Benign lymph nodes showed different mean value, peak intensity and area under the curve compared with their surrounding arteries (P<0.05). But the differences in mean value, rise time, time to peak, peak intensity and the area under the curve between benign lymphadenopathy and their surrounding tissues were not statistically significant (P>0.05). Malignant lymph nodes showed different mean value and peak intensity compared with their surrounding arteries and tissues (P<0.05). The differences in time to peak between malignant lymph nodes and their surrounding tissues were also statistically significant (P<0.05). Conclusion Different CEUS perfusion patterns are associated with different types of lymph node lesions. Time-intensity curves with surrounding tissues as reference condition offer great values for the differential diagnosis of superficial lymphadenopathy.