A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Science in Dentistry Johannesburg, 2015 / Objectives: To analyse the clinico-pathological features of orthokeratinised jaw cysts (OJCs) and to determine whether human papillomavirus (HPV) DNA can be detected in OJCs. Material and methods: The clinical and radiological information of 30 patients diagnosed with OJCs were reviewed and the respective histology samples were studied for light microscopic features characteristic of HPV infection. The 30 OJCs were further evaluated for the presence of HPV by using consensus HPV polymerase chain reaction (PCR). Results: Patients with OJC ranged from 13 to 71-years (mean, 30.9 years; ± 12.9 years). There was a predilection for males (21/30). Most OJCs were found in the mandible (80%) and 44.8% were associated with an impacted tooth. Koilocyte-like characteristics were identified in 70% of cases, while 43.3% of cases showed a verruciform pattern of hyperkeratosis. All 30 OJCs were negative for HPV-DNA. Conclusion: HPV infection does not appear to play a role in the OJC and is not responsible for the wart-like histological changes that may be encountered in OJCs.