In this study the intensity of expression of major histocompatibility complex (MHC) class I and II antigens, adhesion molecule i.e. ICAM-1, epidermal growth factor receptor i.e. EGFr, T cell marker and cytokeratin were compared in oral squamous cell carcinoma (OSCC) and in the benign ameloblastoma of the jaws. The results showed that: a) There was strong expression of both monomorphic and of polymorphic class I MHC antigens (90% of cases) in both basal and suprabasal cells of controls from normal mucose. b) Whereas up to 4% of OSCCs and 27% of ameloblastomas showed complete loss of monomorphic class I antigens, the frequency of polymorphic class I abnormalities was even more marked in both tumour types. c) Strong expression of class II MHC antigens and of ECFr was observed in the basal cells of most normal controls. d) Both class II (50% of cases) and ICAM-1 (30% of cases) showed strong expression in OSCC but not in ameloblastoma. The statistical values between OSCC and normal basal cells for class II and ICAM-1 were not significant whilst the corresponding values for OSCC compared with ameloblastoma were p<0.001 and p<0.001. In the case of OSCC, there were a large number of infiltrating T cells expressing activation marker i.e. class II antigen. e) Strong expression of EGFr was seen in more than 90% of the OSCC cases compared with only 16% of ameloblastomas (0.01<p>0.001). Our working hypothesis to explain these abnormalities is that although both tumour types (more so in the case of ameloblastoma) have in place an escape mechanism from the immune system, the overexpression of EGFr in OSCC may in part be responsible for the more aggressive behaviour of the malignancy compared with the locally invasive but benign ameloblastoma.