In this paper, a new Computer-Aided Detection (CAD) system for the detection and classification of dangerous skin lesions (melanoma type) is presented, through a fusion of handcraft features related to the medical algorithm ABCD rule (Asymmetry Borders-Colors-Dermatoscopic Structures) and deep learning features employing Mutual Information (MI) measurements. The steps of a CAD system can be summarized as preprocessing, feature extraction, feature fusion, and classification. During the preprocessing step, a lesion image is enhanced, filtered, and segmented, with the aim to obtain the Region of Interest (ROI); in the next step, the feature extraction is performed. Handcraft features such as shape, color, and texture are used as the representation of the ABCD rule, and deep learning features are extracted using a Convolutional Neural Network (CNN) architecture, which is pre-trained on Imagenet (an ILSVRC Imagenet task). MI measurement is used as a fusion rule, gathering the most important information from both types of features. Finally, at the Classification step, several methods are employed such as Linear Regression (LR), Support Vector Machines (SVMs), and Relevant Vector Machines (RVMs). The designed framework was tested using the ISIC 2018 public dataset. The proposed framework appears to demonstrate an improved performance in comparison with other state-of-the-art methods in terms of the accuracy, specificity, and sensibility obtained in the training and test stages. Additionally, we propose and justify a novel procedure that should be used in adjusting the evaluation metrics for imbalanced datasets that are common for different kinds of skin lesions.