Background: KAI-1/CD82 is a tumor suppressor gene with decreased gene expression being associated with increased invasive ability of Oral Squamous Cell Carcinoma (OSCC) and as hypothesised for various odontogenic cysts and tumors. p53 protein functions in G1-S phase of the cell cycle to allow the repair of damaged DNA. In the present study, p53 and KAI-1 expression was investigated by using monoclonal antibodies in the various odontogenic cysts. Aims: To detect KAI-1 and p53 expression in Radicular cysts, Dentigerous cysts, and Odontogenic Keratocysts (OKCs) and to assess the relation between p53 and KAI-1 expression in the aforementioned cysts. Materials and Methods: The present study included histopathologically diagnosed cases of Radicular cysts, Dentigerous cysts, and Odontogenic Keratocysts (OKCs) for the expression of KAI-1 and p53 antibodies. Results: Amongst odontogenic cysts, radicular cysts expressed maximum positivity of KAI-1 (20.92%) while p53 positive cells were maximum in odontogenic keratocysts (4.04%). The correlation between KAI-1 and p53 expression in the various odontogenic cysts was not found to be significant. Conclusion: The increased KAI-1 expression in the radicular cysts and its downregulation in OKCs may be indicative of aggressive clinical behavior and the fact that OKCs are hypothesized as neoplastic rather than being developmental in origin.