Introduction <p>p63 is essential for normal proliferation and differentiation of odontogenic epithelium. Since odontogenic keratocyst (OKC), dentigerous cyst (DC) and radicular cyst (RC) are odontogenic epithelial lesions, p63 may play a role in their pathogenesis and biological behaviour. p63 can preserve keratinocytes with stem cell potential by preventing premature apoptosis and terminal differentiation during wound healing.</p> Aim <p>The aim is to explore the role of p63 in pathogenesis, regenerative potential and biological behaviour of various odontogenic cysts.</p> Materials and Method <p>The study involved 40 samples, which are OKC (<i>n</i> = 10), DC (<i>n </i>= 10), RC (<i>n</i> = 10) and regenerating tissue samples (<i>n</i> = 10), are taken as a comparative measure. p63 protein expression was evaluated by immunohistochemistry. (qualitative, quantitative and topography).</p> Result <p>p63 was expressed in basal and parabasal layer in lining epithelium of OKC. In addition, p63 was expressed throughout the lining epithelium in RC and DC.</p> Conclusion <p>The present study suggests that p63 overexpression is associated with increased proliferation. Thereby, p63 can be a prognostic biomarker in odontogenic lesions with aggressive phenotype. Henceforth, discerning the pathogenesis of developmental and inflammatory cysts is critical for determining the surgical approach and predicting the prognosis of odontogenic cysts.</p>