INTRODUCTION: Odontogenic keratocyst (OKC) is a developmental odontogenic cyst with distinct pathological features and a high recurrence rate. Interest among OKCs became apparent by the clinical challenges associated with their treatment. Pathogenesis of OKCs is a multifactorial process, which is linked to several signalling pathways and expression of stem cell markers such as SOX2 and OCT4. MATERIALS AND METHODS: Thirty cases of OKCs were categorised into three groups: primary (n = 10), recurrent (n = 10), and decompressed (n = 10). Tissue sections were immunohistochemically stained using anti-SOX2 and anti-OCT4 antibodies. Staining distribution, intensity, and localisation were evaluated qualitatively. Quantitative assessment was performed using Image Pro Plus software, and statistical analysis was conducted using SPSS software and results were statistically analysed. RESULTS: SOX2 expression was observed in 80% of primary, 80% recurrent, and 90% of decompressed OKCs, with significant differences in staining intensity ( = 0.032). Most cases exhibited diffuse, nuclear, and cytoplasmic positivity across the full epithelial thickness, particularly in suprabasal layers. OCT4 expression was limited to 10% of primary and 20% of recurrent OKCs, with no positivity observed in decompressed cases. OCT4 did not show statistically significant differences. Remmele scores for both markers were not statistically significant across the groups. CONCLUSION: High expression of SOX2 in OKCs supports its role as a marker of epithelial stemness and a potential biomarker for aggressive behaviour and recurrence. Limited expression of OCT4 suggests a minimal role in OKC pathobiology, possibly associated with early differentiation. Lack of OCT4 expression in decompressed lesions raises questions about the molecular efficacy of decompression therapy.