Background: The role of histopathology as a tool in diagnosing chronic osteomyelitis (COM) in Ghana has not been evaluated. The aim of this study was to evaluate the importance of histopathology as a tool in diagnosing and describing the clinicopathological features of COM in sequestrectomy and other small biopsy specimens. Material and methods: The following data on 75 patients with COM were collected: age, gender, primary and associated symptoms, history of prior trauma and the use of herbal treatment. The data was analysed using SPSS software version 26.0 (Chicago). Descriptive statistics were used to describe the data. Fisher’s exact test was used to compare clinical variables of significance. Results: The median age of the patients was 12.0 years, with a male: female ratio of 2:1. The commonest primary presentation was a painful swelling 55 (73.3%, p<0.001). The sites commonly involved were: tibia (34.7%), femur (22.7%) and hip joint (10.7%). Approximately, 84.8% (p<0.001) of those with additional complains had a discharging sinus. A total of 27 (36.0%) patients had history of prior trauma, while, 41 (54.6%) had history of prior use of herbal treatment. There was a significant association between discharging sinus tract and the use of herbal medicine (P= 0.009). There was also an association between trauma and herbal medicine usage (p = 0.011). Conclusion: Chronic osteomyelitis commonly affect young males, with the long bones of the axial skeleton being the common site of infection. Prior trauma and the use of herbal medicine for fracture managements were the common risk factors.