Background: To enhance the clinical evaluation of pigmented skin lesions (PSL), examination of PSL at a high magnification and computer-aided diagnosis have been introduced. Besides surface microscopes, “videomicroscopes” that are provided with polarized light are commercially available. Images recorded in the polarizing mode are comparable with those obtained after application of a drop of oil and a glass slide. Objective: The purpose of this study was to evaluate the usefulness of a digital videomicroscope equipped with a dedicated program for the diagnosis of melanocytic PSL by assessing the digital features referring to benign and malignant PSL images and by comparing the clinical assessment performed on 20-fold magnified images to computer diagnosis that were provided by the discriminant analysis calculation carried out on the numeric values describing the images. Methods: Nine hundred seventeen melanocytic PSL images, corresponding to 852 nevi and 65 melanomas, were considered. For microscopic examination, a 10- (39 cases), 20- (501 cases), or 50-fold magnification (377 cases) was chosen according to the size of the lesion, enabling the whole lesion to be seen on the monitor. All digital images were framed and analyzed with software that calculates different features related to the geometry, color distribution, and internal pattern of the lesion. Features referring to benign and malignant PSL were compared. Moreover, 90 PSL images recorded by a ×20 magnification, corresponding to 59 benign PSL and 31 malignant melanomas, were evaluated by 2 observers, 1 observer experienced in videomicroscopy and 1 observer, an untrained dermatologist. Sensitivity and specificity were estimated for observer assessment and computer diagnosis. Results: Significant differences between values referring to benign and malignant PSL were observed for most numeric features. Sensitivity was higher for the computer assessment and lower for the inexperienced observer, whereas specificity was the same for the computer and the trained observer. Conclusion: Numeric features referring to benign PSL significantly differ from those of malignant PSL images. Elaboration of videomicroscopic images by means of a dedicated program improves diagnostic accuracy over the simple examination of pigmented skin lesions by means of magnifying and polarizing systems. (J Am Acad Dermatol 1998;39:175-81.)