Optimizing example-based computer-aided diagnosis (CADx) is accomplished by clustering volumes-of-interest (VOIs) (116) in a database (120) into respective clusters according to subjective assessment of similarity (S220). An optimal set of volume-of-interest (VOI) features is then selected for fetching examples such that objective assessment of similarity, based on the selected features, clusters, in a feature space, the database VOIs so as to conform to the subjectively-based clustering (S230). The fetched examples are displayed alongside the VOI to be diagnosed for comparison by the clinician. Preferably, the displayed example is user-selectable for further display of prognosis, therapy information, follow up information, current status, and/or clinical information retrieved from an electronic medical record (S260).