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Background: These stemness markers have proved their ability in tumorigenicity, tumor metastasis, and even distant recurrence after chemotherapy in different types of cancer. Also, it has shown its evidence in pre-malignant conditions such as OSMF (Oral Submucous Fibrosis) did show the presence of stem cell markers such as Sox2 and Oct4.  Aim: Establishing the relationship of Sox2 and Oct4 markers with a potentially malignant disorder, OSMF. Correlation between the said markers and the clinical and histopathological classification. Materials and Methods: 40 archival tissue samples of OSMF were clinically and histopathologically classified using Khanna and Andrade classification. Immunohistochemical analysis for Sox2 and Oct4 was performed on paraffin-embedded tissue sections on 20 histopathologically confirmed cases of oral submucous fibrosis each. Results: The resulting data were analyzed using the SPSS software version 20.0. The significance of the parameters was tested by the Pearson's Chi-square test (P ≤ 0.05 as statistically significant). The immunohistochemical results showed that Sox2 and Oct4 could be detected in the basal and suprabasal layers in OSMF. Although no significant difference was noted in the expression of Sox2 and Oct4 with increasing grades of oral submucous fibrosis Conclusion: The results obtained from this study show a contingency between the Sox2 and Oct4 marker with OSMF. These results need to be further investigated and further verified with the inclusion of a greater number of cases.

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