Medical educators agree that empathy is essential for physicians' professionalism and most studies on the patient-physician relationship demonstrate that this attitude has a key role in improving clinical outcomes. Literature findings show conflicting views in defining and measuring empathy. Nevertheless, the Jefferson Scale of Empathy (JSE) is a psychometric tool now widely used. Therefore, the aim of this study was to examine psychometrics and confirm factor structure of the Italian version of the JSE in Italian medical students (JSE S-Version). During 2012, 257 second-year Italian medical students completed the JSE S-Version. Internal consistency and test-retest reliability were assessed. A confirmatory factor analysis was performed to test the factor structure. The Italian JSE S-Version showed an acceptable internal consistency (r = 0.76) and test-retest reliability (r = 0.72). Confirmatory factor analysis found that the factor structure proposed by the developers of the tool provides an acceptable data fit. In this sample, female medical students showed a higher mean empathy score than did males. The present study provides evidence confirming the structural validity and reliability for the Italian JSE S-Version. Further studies are needed to confirm these findings and to explore cross-cultural differences and their implications.