Objectives The purpose of this study was to prospectively assess the diagnostic efficacy of contrast-enhanced sonography for differential diagnosis of sub-1-cm breast lesions. Methods Contrast-enhanced sonography was performed in 46 women with 46 sub-1-cm breast lesions scheduled for surgery or biopsy. Histologic results were used as a reference standard. The contrast enhancement pattern, enhancement degree, direction, margin, radial vessels surrounding the lesion, and lesion size discrepancy-between contrast-enhanced and conventional sonography were evaluated. Results The detection rates for increased size, radial vessels surrounding the lesion, and hyperenhancement on contrast-enhanced sonography were significantly higher in the malignant than the benign group (P <.05). The sensitivity, specificity, and accuracy for increased size were 72.7%, 80.0%, and 78.2%, respectively. The sensitivity, specificity, and accuracy for radial vessels surrounding the lesion were 54.5%, 97.1%, and 87.0%. The sensitivity, specificity, and accuracy for hyperenhancement were 81.8%, 60.0%, and 65.0%. No significant difference was found for the enhancement pattern, direction, and margin between the groups. Conclusions Contrast-enhanced sonographic features of sub-1-cm breast lesions included increased size on contrast-enhanced sonography, radial vessels surrounding the lesion, and hyperenhancement. Identification of these features is useful for differentiation of small breast lesions.