Objective To evaluate the real-time contrast-enhanced ultrasonography (CEUS) in the differential diagnosis of retroperitoneal occupying lesions. Methods Thirty patients with retroperitoneal occupying lesions, including 10 benign and 20 malignant lesions, were performed with CEUS, thus describing the perfusion of contrast agent, the entering style of contrast agent and the vascular morphous. And the entering styles were divided into two patterns: peripheral type or central type while the vascular morphous were divided into 4 levels: level 0, level 1, level 2 and level 3. All of these were compared between benign and malignant lesions. Compared the results of diagnosis malignant lesions by common ultrasonography with CEUS. Results 1/5 case of benign substantive lesions presented as contrast agent perfusion defect, and 11/20 cases of substantive malignant lesions presented as contrast agent perfusion defect. 14/20 of malignant lesions were central type; 9/10 of benign lesions were peripheral type (P=0.005 2). In benign lesions, level 0 had 7/10， level 1 had 2/10 and level 3 had 1/10. In malignant lesions, level 0 had 1/20, level 1 had 3/20, level 2 had 8/20 and level 3 had 8/20, too (P=0.000 5). The rate of missed diagnosis was 40.00% and the accuracy was 66.67% by common ultrasonography, while the rate of missed diagnosis was 10.00% and the accuracy was 86.67% by CEUS combined with the entering style of contrast agent and the vascular morphous. Conclusion The CEUS applies a new way to discriminate malignant from benign in retroperitoneal occupying lesions.