In 2005 the World Health Organisation classified the odontogenic keratocyst (OKC) as a benign cystic neoplasm, using the term keratocystic odontogenic tumour. Significantly higher expression of proto-oncogenes and loss of expression of tumour suppressor genes have been demonstrated in the OKC when compared to more indolent jaw counterparts. This together with the higher mitotic activity in the epithelial lining of OKC could explain the aggressive behaviour of the OKC consistent with that of benign neoplasms. The BCL-6 proto-oncogene was identified in 1993 as a transcription factor whose deregulated expression is associated with B-cell non-Hodgkin lymphomas. In epithelial neoplasms, the BCL-6 transcription factor is associated with continuous growth and its absence triggers apoptosis. It has been suggested that BCL-6 may also participate prominently in the process of differentiation of epithelial cells. The aim of the study was to evaluate BCL-6 protein expression in the dentigerous cyst (n=10), radicular cyst (n=10) and OKC (n=20) by immunohistochemistry. Expression of BCL-6 was significantly higher in the OKC than in the dentigerous cyst and radicular cyst. In the OKC BCL-6 further showed a distinct predilection for the suprabasal compartment while in the dentigerous and radicular cysts the staining tended to be uniform throughout all the cell layers of the cyst lining. The study findings suggest that BCL-6 may play a role in the regulation of the suprabasal proliferative compartment of the OKC and in the keratinising epithelial cell differentiation of the OKC.