This study assessed the efficacy of percutaneous contrast-enhanced ultrasound (CEUS) in localization sentinel lymph node (SLNs) for biopsy and diagnosis of metastatic SLNs in patients with early breast cancer. From January to November 2017, seventy-five patients with early breast cancer confirmed by pathology were enrolled in this study. CEUS was performed after subdermal injection of ultrasound contrast agent (SonoVue, 2.0 ml in total dose) around the areola on the ipsilateral side of the breast. The contrast-enhanced lymphatic vessels and associated SLNs were observed and traced in real time. The lymphatic vessels and SLN were mapped and labeled on the skin surface. Sentinel lymph node biopsy (SLNB) was performed after injection of 2.0 ml methylene blue at same injection site of SonoVue. The accuracy of percutaneous CEUS localization of SLNs was determined compared to blue dye injection technique. The pathological results under blue dye guided biopsy were used as the reference standard to calculate the sensitivity and specificity of CEUS for the diagnosis of SLNs. A total of 163 SLNs obtained through SLNB following methylene blue tracing in 75 patients. There were 116 SLNs identified by percutaneous CEUS. The difference of detection rates between blue dye and CEUS was statistically significant (Z = -2.651, P = 0.008). The identification rate of SLNs by CEUS was 71.17% (116/163). The accuracy of percutaneous CEUS localization of axillary SLNs was 94.67% (71/75) compared to blue dye-guided biopsy. Among the 116 SLNs detected by percutaneous CEUS, pathologic results showed 51 positive SLNs and 65 negative SLNs whiles CEUS findings indicated 83 positive SLNs and 33 negative SLNs. Only 50 of 83 SLNs had metastasis on pathology, while 33 were detected as false positive. The sensitivity and specificity of CEUS for the diagnosis of metastatic SLN was 98.04%(50/51) and 49.23%(32/65), respectively. Percutaneous CEUS can be used as an effective method to localize the SLNs for guiding SLNB. This method has excellent sensitivity for identifying the SLNs but lower specificity for detecting metastatic SLNs in patients with early stage breast cancer.