In this paper we investigate several state-of-the-art machine-learning methods for automated classification of clustered microcalcifications (MCs), aimed to assisting radiologists for more accurate diagnosis of breast cancer in a computer-aided diagnosis (CADx) scheme. The methods we consider include: support vector machine (SVM), kernel Fisher discriminant (KFD), and committee machines (ensemble averaging and AdaBoost), most of which have been developed recently in statistical learning theory. We formulate differentiation of malignant from benign MCs as a supervised learning problem, and apply these learning methods to develop the classification algorithms. As input, these methods use image features automatically extracted from clustered MCs. We test these methods using a database of 697 clinical mammograms from 386 cases, which include a wide spectrum of difficult-to-classify cases. We use receiver operating characteristic (ROC) analysis to evaluate and compare the classification performance by the different methods. In addition, we also investigate how to combine information from multiple-view mammograms of the same case so that the best decision can be made by a classifier. In our experiments, the kernel-based methods (i.e., SVM, KFD) yield the best performance, significantly outperforming a well-established CADx approach based on neural network learning.