OBJECTIVE: The aim of this study was to establish a possible association between the degree of differentiation of squamous cell carcinomas (SCC) derived from rat oral tissues treated in vivo with the carcinogen 4NQO, and the expression of TGF‐β on epithelial cells and the distribution of extracellular matrix proteins (laminin‐collagen type IV).MATERIALS AND METHODS: A parent tumour showing a spectrum of differentiation was used to establish clonal subpopulations that formed differentiated SCC and undifferentiated (spindle cell phenotype) tumours following transplantation to athymic mice.RESULTS tmmunohistological findings revealed the absence of TGF‐β staining on epithelial cells and extracellular matrix proteins in spindle cell tumours. In contrast, staining of SCC revealed a significant number of TGF‐β positive cells and the presence of extracellular matrix proteins.CONCLUSIONS: The findings suggested that there is a positive correlation between histological differentiation, TGF‐β expression and the elaboration of extracellular ma