Background: Oral squamous cell carcinoma (SCC) develops from pre-malignant lesions, but the role of cell adhesion molecules such as E-cadherin (E-CD) and P-cadherin (P-CD) in the pre malignant stage has not been elucidated. Methods: The expression of E-CD and P-CD was examined immunohistochemically and biochemically in a 4-nitroquinoline 1-oxide (4NQ0)-induced rat model of carcinogenesis. Results: The expression of E-CD in the pre-malignant stage was the same as that in the normal epithelium. The expression of PCD was even throughout the prickle cell layer in the dysplasia stage. E-CD and P-CD were expressed in essentially the same locations in SCC and in the pre-malignant stage. P-CD expression was very strong in the pre-malignant stage, compared to that in normal epithelium. Conclusions: Aberrant P-CD expression in E-CD-positive cells may play a crucial role in the progression of the pre-malignant stage of 4NQO-induced carcinogenesis, and may activate mechanisms responsible for cell proliferation.