Based on these new technologies, the embalmed body of Ferrante Gonzaga (1507–1557), an Italian noblemen of the Renaissance period, was CT scanned and the digital three-dimensional data were used for virtual anthropological analysis. A physical model of the skull was obtained by rapid prototyping technique and used for facial reconstruction according to forensic art methods. Finally, the reconstructed face was compared with two portraits of Ferrante Gonzaga (Uffizi and Ambras portraits) using a virtual skull-painting superimposition technique. Despite the limits of the superimposition method when dealing with historical portraits in fronto-lateral view, our results pointed out more similarities with the Ambras portrait. By means of this multi-disciplinary approach, doubts regarding the reliability of historical portraits could be resolved.