We present a novel image-analysis based method for automatically distinguishing low, intermediate, and high grades of breast cancer in digitized histopathology. A multiple level feature set, including pixel-,object-,and semantic-level features derived from convolutional neural networks (CNN), is extracted from 106 hematoxylin and eosin stained breast biopsy tissue studies from 106 women patients. These multilevel features allow not only characterization of cancer morphology, but also extraction of structural and interpretable information within the histopathological images. In this study, an improved hybrid active contour model based segmentation method was used to segment nuclei from the images. The semantic level features were extracted by a CNN approach, which described the proportions of nuclei belonging to the different grades, in conjunction with pixel-level (texture) and object-level (architecture) features, to create an integrated set of image attributes that can potentially outperform either subtype of features individually. We utilized a cascaded approach to train multiple support vector machine (SVM) classifiers using combinations of feature subtypes to enable the possibility of maximizing the performance by leveraging different feature sets extracted from multiple levels. Final class (cancer grade) was detertnined by combining the scores produced by the individual SVM classifiers. By employing a light (three-layer) CNN model and parallel computing, the presented approach is computationally efficient and applicable to large-scale datasets. The method achieved an accuracy of 0.92 for low versus high, 0.77 for low versus intermediate, and 0.76 for intermediate versus high, and an overall accuracy of 0.69 when discriminating low, intermediate, and high grades of histopathological breast cancer images. This suggested that our grading method could be useful in developing a computational diagnostic tool for differentiating breast cancer grades, which might enable objective and reproducible alternative for diagnosis. (C) 2016 Elsevier B.V. All rights reserved.