High mobility group B (HMGB) chromosomal proteins, which plays important role in cancer and inflammation, were followed at various stages of the squamous cell carcinoma of skin. Present results were analyzed by histopathology, BrdU assay, immunohistochemistry, western blot and RT-PCR, which indicate that at early stages of tumorigenesis, expression of HMGB (B1, B2), raised only by about 20%. However, the advanced (> or =12 weeks) tumors showed significant (> or =80%) increase in HMG levels. Using skin cancer model, we demonstrated that high levels of HMGB directly correlate with the extent of neoplastic changes, and it appears that HMGB is an effective stimulus for cell differentiation, tumor progression, and metastatic invasion.