Medical imaging systems are very important in medicine domain. They assist specialists to make the final decision about the patient’s condition, and strongly help in early cancer detection. The classification of mammogram images represents a very important operation to identify whether the breast cancer is benign or malignant. In this chapter, we propose a new computer aided diagnostic (CAD) system, which is composed of three steps. In the first step, the input image is pre-processed to remove the noise and artifacts and also to separate the breast profile from the pectoral muscle. This operation is a difficult task that can affect the final decision. For this reason, a hybrid segmentation method using the seeded region growing (SRG) algorithm applied on a localized triangular region has been proposed. In the second step, we have proposed a features extraction method based on the discrete cosine transform (DCT), where the processed images of the breast profiles are transformed by the DCT where the part containing the highest energy value is selected. Then, in the feature’s selection step, a new most discriminative power coefficients algorithm has been proposed to select the most significant features. In the final step of the proposed system, we have used the most known classifiers in the field of the image classification for evaluation. An effective classification has been made using the Support Vector Machines (SVM), Naive Bayes (NB), Artificial Neural Network (ANN) and k-Nearest Neighbors (KNN) classifiers. To evaluate the efficiency and to measure the performances of the proposed CAD system, we have selected the mini Mammographic Image Analysis Society (MIAS) database. The obtained results show the effectiveness of the proposed algorithm over others, which are recently proposed in the literature, whereas the new CAD reached an accuracy of 100%, in certain cases, with only a small set of selected features.