Phosphotyrosine (pTyr) is the product of activation of Epidermal Growth Factor receptor (EGFr) in normal and neoplastic oral keratinocytes. As previous studies revealed that EGFr expression may vary with differentiation in several squamous cell carcinomas (SCC), we investigated the expression of pTyr in 30 cases of oral SCC in which EGFr-immunoreactivity had been previously studied. This study was carried out with monoclonal antibodies using an immunohistochemical APAAP method on formalin-fixed, paraffin-embedded samples. The results of this study show that pTyr is expressed in all cases of oral SCC and that its expression is not correlated with tumor differentiation. The Authors suggest that the mechanism of EGFr-mediated cell differentiation and mitosis might short-circuit EGFr in some instances and lead to the phosphorilation of Tyrosine, probably following the stimulation by other factors. This hypothesis needs to be confirmed by appropriate studies on the dynamic biology of oral squamous cells.