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Objective: The aim of the present study was to determine and compare the expression pattern and localization of nestin, in an attempt to explore its role in oral carcinogenesis. Methods: Western blot and immunohistochemistry analysis were performed to study the expression pattern of nestin in normal mucosa, leukoplakia, and oral squamous cell carcinoma samples. Nestin expression was evaluated in the keratinocytes and blood vessels of all the samples and compared with various clinico-pathological parameters. Results: Nestin expression was increased in samples of leukoplakia and oral squamous cell carcinoma when compared with normal mucosa. Among leukoplakia samples, the expression was increased in cases without dysplasia compared to cases with dysplastic features. In cases of oral squamous cell carcinoma, the expression of nestin was found to be decreased with the loss of differentiation. Neoangiogenesis status determined by nestin expression showed an increasing expression from normal mucosa through leukoplakia, to oral squamous cell carcinoma. Conclusion: This study has two major findings: (1) identification of nestin as an effective indicator of neoangiogenesis, and (2) nestin may be used as a marker in predicting the early changes in oral carcinogenesis. [ABSTRACT FROM AUTHOR]