The role of dysplastic oral pre-cancers in oral squamous cell carcinoma development is well recognized, but the notion is not exclusive. Diagnostic gold standards in predicting malignant potentiality of such pre-cancers suffer from ambiguity due to inter- and intra-observer variability. In addressing such diagnostic challenges, combinatorial appraisement of molecular pathology attributes encompassing cancer hallmarks is thought to provide a wider analytical sense. Two major premalignant disorders, viz. oral leukoplakia and oral submucous fibrosis have been considered as candidate precursors of cancer here. This review highlights the molecular pathology signatures expressed in oral epithelial dysplasia and revisits the usefulness of combinatorial analysis of expressional pattern of existing molecular biomarkers in the context of proper selection of cardinal attributes from each cancer hallmark for better malignant potentiality assessment.