Objectives. To investigate the value of contrast-enhanced ultrasound (CEUS) in guidance of percutaneous biopsy in peripheral pulmonary lesions. Methods. This study focused on 53 patients (male: 38, female: 15, and mean age: 55.7 years ± 10.7) with 53 single peripheral pulmonary lesions. Before core needle (16-gauge) percutaneous biopsy, CEUS were performed in all lesions, with injection of 2.4 mL SonoVue (Bracco, Italy). The contrast-enhancement pattern, display rate of internal necrosis (nonenhanced) and active (obviously enhanced) areas, biopsy success rate, and pathological diagnosis rate were recorded. Results. All the peripheral pulmonary lesions were proved pathologically as benign lesions (n=7), primary malignancies (n=41), or metastasis (n=5). Forty (86.9%) malignant lesions and 4 (57.1%) benign lesions showed internal necrosis areas on CEUS. The detection rate and average size of internal necrosis areas had been significantly improved compared to conventional ultrasound (P<0.05). After CEUS, core needle percutaneous biopsies were performed successfully in the active areas of all lesions. The sampling success rate and pathological diagnosis rate were 100% and 98.1%. Conclusions. CEUS before biopsy provided useful diagnostic information about peripheral pulmonary lesions. By depicting internal necrotic and active areas, it is a promising technique for guaranteeing the accuracy, success, and safety of core needle biopsy.