Objective To determine the clinical value of bone tumor biopsy guided by contrast-enhanced ultrasound(CEUS).Methods A total of 105 patients with bone tumor intended undergo core needle biopsy were divided into two groups, two-dimensional ultrasound guide core need biopsy(US-CNB) group and contrast-enhanced ultrasound guide core need biopsy group(CEUS-CNB), compared the operating time and biopsy number. Pathological results or clinical comprehensive diagnosis were regarded as the gold standard, compared the diagnostic sensitivity and specificity, positive predictive value, negative predictive value and diagnostic accuracy between the two groups. Receiver operating characteristic(ROC) curves of US-CNB group and CEUS-CNB group were drawn and the area under the curve was calculated. Results There was no significant difference in operating time and biopsy number between the two groups（P=0.913，P=0.854）.The diagnostic specificity and accuracy of the CEUS-CNB group were higher than that of the US-CNB group（P=0.038，P=0.031），and the diagnostic sensitivity，positive predictive value and negative predictive value of the CEUS-CNB were higher than the US-CNB group，but there were no statistical differences（P=0.419，P=0.053，P=1.000）.In the ROC curve analysis of the CEUS-CNB group was 0.977，and the US-CNB group was 0.865.Conclusion CEUS can achieve higher diagnostic specificity and accuracy than US guided biopsy for bone tumors with soft mass.