Background: The assessment of malignant potential of oral submucous fibrosis grades vis-à-vis their progression towards malignancy is associated with expression of possible multiple molecular markers. Aims: To analyse p63, E-cadherin and CD105 expression in this premalignant pathosis with a view to unravel and understand the expression of these molecules as markers. Methods: The oral mucosal biopsies (normal, oral submucous fibrosis with and without dysplasia) were studied with routine H&E, and by immunohistochemistry for p63, E-cadherin and CD105 expression. p63 was assessed as percentage of positive nuclei. E-cadherin expression was estimated through (i) distance between basement membrane and E-cadherin expression initiation point, (ii) ratio between epithelial thickness and epithelial thickness displaying E-cadherin, and (iii) E-cadherin intensity variation along the expression path. CD105 expression was assessed qualitatively. Results: The p63+ cells were highest in severely dysplastic tissues followed by other dysplastic grades, normal oral mucosa and non-dysplastic conditions. However, the p63+ cells displayed the feature of progressive maturation only in normal mucosa. There was a loss of membranous E-cadherin in basal layers of all diseased conditions; it was highest in severe dysplasia. There was significant variation (p<0.0001) in E-cadherin intensity within and between the tissues (normal and diseased). CD105 expression increased abruptly in dysplasia. Conclusions: The malignant potential of this pre-cancerous condition is likely to be correlated with an increase in p63 and CD105 expression and a concomitant loss of membranous E-cadherin. This may lead to marker identification through greater validation.