Purpose To investigate the value of contrast-enhanced ultrasound (CEUS) in guidance of percutaneous biopsy in anterior mediastinal lesions.Methods and Materials The study focused on 60 patients (male 35,female 25,mean age,41 years ± 3) with 60 single anterior mediastinal lesions detected on contrast-enhanced CT.Before biopsy,patients were randomly divided into CEUS group (n =30) and conventional ultrasound group (n =30).CEUS were performed with injection of 2.4mi SonoVue(R) (Bracco,Italy).Core needle (16 Gauge) percutaneous biopsies were performed in all lesions.The display rate of internal necrotic (unenhanced) areas,active (obviously enhanced) areas and internal mammary arteries,biopsy success rate and pathological diagnosis rate were recorded and compared between two groups.Results The mean maximum diameter of anterior mediastinal lesions was 61.2 ± 5.4mm (mean + SD),all lesions were proved histologically.In CEUS group,85.7 % (30/35) lesions showed unenhanced internal necrotic areas,which was higher than conventional ultrasound (60.0 %,15/25,P < 0.05).Internal mammary arteries were effectively avoided during biopsies in 60.0 % (21/35) cases of CEUS group.Biopsies sampling the active areas demonstrated on CEUS had 100 % success rate and 96.4 % pathological diagnosis rate,which were higher than conventional ultrasound guided group (85.3 % and 81.2 %,P < 0.05).Conclusions By depicting internal necrotic areas,active areas and internal mammary arteries,CEUS guided biopsy of anterior mediastinal lesion is a promising technique with accuracy,safety and success.