Background: Understanding the socio-cultural factors that underlie homicide is central to prevention of such cases. This study was carried out to determine the similarities and differences in the patterns of homicide in two socio-culturally diverse parts of Nigeria. Materials and Method: Duplicate copies of autopsy reports of homicide victims in Port Harcourt, Rivers State and Kano city, Kano State over 11 and 6 year periods respectively were retrieved and analyzed for age, gender, circumstances of death, mechanisms of death, causes of death and types of weapons used. Results: show that 1,004 cases (91/year rate) and 113 cases (18/year rate) of homicides were recorded respectively in Port Harcourt and Kano city during the study periods. The predominant age group of victims in the two cities was the 21 to 30 year age group, with male: female ratio of 12:1 and 16:1 for Port Harcourt and Kano city respectively. The top ranking weapons of choice were firearm (68.9%) in Port Harcourt and sharp daggers (44.2%) in Kano city. While armed robbery and cult attacks were common in Port Harcourt, ethno-religious clashes predominated among circumstances surrounding homicides in Kano. While head injuries in the Port Harcourt homicides were mostly from gunshots those in Kano city were mostly due to blunt trauma. Conclusion: This study has shown that socio-cultural differences in religion, type of weapons available and to which local residents are exposed to during upbringing, gender role, functional rule of law, use of psycho-active substances and increased population and its dynamics are important factors that determine patterns of homicide in Nigeria.