High false-positive recall rate is an important clinical issue that reduces efficacy of screening mammography. Aiming to help improve accuracy of classification between the benign and malignant breast masses and then reduce false-positive recalls, we developed and tested a new computer-aided diagnosis (CAD) scheme for mass classification using a database including 600 verified mass regions. The mass regions were segmented from regions of interest (ROIs) with a fixed size of 512×512 pixels. The mass regions were first segmented by an automated scheme, with manual corrections to the mass boundary performed if there was noticeable segmentation error. We randomly divided the 600 ROIs into 400 ROIs (200 malignant and 200 benign) for training, and 200 ROIs (100 malignant and 100 benign) for testing. We computed and analyzed 124 shape, texture, contrast, and spiculation based features in this study. Combining with previously computed 27 regional and shape based features for each of the ROIs in our database, we built an initial image feature pool. From this pool of 151 features, we extracted 13 features by applying the Sequential Forward Floating Selection algorithm on the ROIs in the training dataset. We then trained a multilayer perceptron model using these 13 features, and applied the trained model to the ROIs in the testing dataset. Receiver operating characteristic (ROC) analysis was used to evaluate classification accuracy. The area under the ROC curve was 0.8814±0.025 for the testing dataset. The results show a higher CAD mass classification performance, which needs to be validated further in a more comprehensive study.