To evaluate the usefulness of contrast-enhanced ultrasonography (CEUS) in differentiating malignant from benign peripheral pulmonary lesions, and to evaluate the feasibility, accuracy, and utility of CEUS-guided biopsy for peripheral pulmonary lesions. MATERIALS AND METHODS: Thirty-three patients with histopathologically confirmed peripheral pulmonary lesions (22 malignant, 11 benign) were enrolled in this retrospective study. Conventional ultrasound (US) was first performed and then CEUS with a contrast-specific mode and sulfur hexafluoride-filled microbubble contrast agent. CEUS indicesdtime of enhancement (TE), time to peak (TP), extent of peak (EP), mean transit time (MTT), area under curve (AUC), and slopedwere recorded and compared between the groups. The ability of CEUS and US to detect necrotic areas within lesions was also compared and the accuracy of CEUS-guided biopsy was calculated. RESULTS: On CEUS, TE was significantly shorter in acute pneumonia lesions than in other types of lesions (p¼0.03). Other indices were not significantly different between benign and malignant lesions. Detection of necrosis within lesions was significantly higher with CEUS than with US (51.5% versus 27.3%; p¼0.04). The accuracy of CEUS-guided biopsy was 96.9% (32/33). CONCLUSION: The study findings suggest that CEUS can identify necrotic areas within lesions, and thereby, play a useful role in imaging-guided biopsy. The present pilot study indicates that CEUS may help to identify acute pneumonia lesions from other types of pulmonary lesions. CEUS might be a useful additional technique for the diagnosis of lung lesions.