This study analyzes postmortem records from 260 homicide cases autopsied by the Department of Forensic Medicine in Rome from 2000 to 2014. The victims were mainly males (74%) and young (61% aged from 21 to 50 years). Although the victims were mostly Italians, the number of foreign victims (33%) has increased since 1990, primarily due to immigration. The offenders frequently used firearms (39%), particularly in multiple murders. An increase in blunt (20%) and sharp force (32%) weapons was also seen. The primary crime scene was residential (42%), and the head was the most frequently injured body region. Male victims occurred frequently in the context of organized crime (7.6%). In family or intimate-sexual relationships, women were the majority of victims (8%). Forensic pathologists play an important role during investigation. They should consider all the information available to them, including autopsy information, crime scene information, and crime investigation data.