To retrospectively evaluate the accuracy of neural network analysis of tumor vascular features at three-dimensional (3D) power Doppler ultrasonography (US) for classification of breast tumors as benign or malignant, with histologic findings as the reference standard. This study was approved by the local ethics committee; informed consent was waived. Three-dimensional power Doppler US images of 221 solid breast masses (110 benign, 111 malignant) were obtained in 221 women (mean age, 46 years; range, 25-71 years). After narrowing down vessels to skeletons with a 3D thinning algorithm, six vascular feature values--vessel-to-volume ratio, number of vascular trees, total vessel length, longest path length, number of bifurcations, and vessel diameter-were computed. A neural network was used to classify tumors by using these features. Independent-samples t test and receiver operating characteristic (ROC) curve analysis were used. Mean values of vessel-to-volume ratio, number of vascular trees, total vessel length, longest path length, number of bifurcations, and vessel diameter were 0.0089 +/- 0.0073 (standard deviation), 26.41 +/- 14.73, 23.02 cm +/- 19.53, 8.44 cm +/- 10.38, 36.31 +/- 37.06, and 0.088 cm +/- 0.021 in malignant tumors, respectively, and 0.0028 +/- 0.0021, 9.69 +/- 6.75, 5.17 cm +/- 4.78, 1.68 cm +/- 1.79, 6.05 +/- 7.55, and 0.064 cm +/- 0.028 in benign tumors, respectively (P < .001 for all six features). Area under ROC curve (A(z)) values of the six features were 0.84, 0.87, 0.87, 0.82, 0.84, and 0.75, respectively. Accuracy, sensitivity, specificity, and positive and negative predictive values were 85% (187 of 221), 83% (96 of 115), 86% (91 of 106), 86% (96 of 111), and 83% (91 of 110), respectively, with A(z) of 0.92 based on all six feature values. Three-dimensional power Doppler US images and neural network analysis of features can aid in classification of breast tumors as benign or malignant.