Familicide, an extreme form of domestic violence where one family member kills another, is a complex criminological issue. We analyzed autopsy files from the Institute of Legal Medicine, University of Rome Tor Vergata (1995–2022), to understand familicide better. The study focused on victim profiles, offender characteristics, and case dynamics. From 29 analyzed cases, 31 victims emerged, with 2 instances of double homicide. The perpetrators were mostly male (79.31%) and the victims were primarily female (54.84%). The familial ties ranged from parent–child to siblings and spouses. A significant number of crimes happened at private residences (70.97%) using bladed weapons (48.39%), with the injuries being concentrated on the head and chest. Half of the cases showed struggle signs, and 24.14% of the perpetrators had identifiable psychiatric disorders, which often served as the motive. Post-crime actions included self-reporting, suicide attempts, and successful suicides. A comparison with literature confirmed the typical familicide offender as a middle-aged male with potential social stressors and a history of domestic violence, with the victims often being female family members. Mental health conditions including depression, bipolar disorder, and schizophrenia significantly impacted these events. These findings underline the need for customized approaches to comprehending and preventing familicide.