To understand the role of 70 kDa heat shock protein (HSP70) in the pathogenesis of oral cancer, its expression was studied in human normal, premalignant and malignant oral mucosa. Cell surface expression of HSP70 was assessed in oral tissue specimens by flow cytometric analysis using a mouse monoclonal antibody against HSP70. A significant increase in cell surface expression of HSP70 was observed as the tissue progressed from normal to dysplasia towards carcinoma. Correlation of HSP70 expression with clinicopathological features showed a positive association with the severity of dysplasia. Among the oral tumours assessed, a significantly positive association was observed between HSP70 expression and dedifferentiation of oral squamous cell carcinomas (SCCs). Poorly differentiated tumours showed significantly higher levels of HSP70 expression on the surface of tumour cells, compared with well differentiated carcinomas (P < 0.05). Cell surface expression of HSP70 was observed to be significantly higher in clinically advanced stage tumours (T3/T4), compared with T1/T2 stage tumours (P < 0.05). The variation in cell surface expression of HSP70 in normal, dysplastic and malignant oral lesions suggests that it is differentially expressed during oral tumorigenesis and may play a specific role in the pathogenesis of oral cancer.