Aim of the present study was to investigate the immunocytochemical expression of Epidermal Growth Factor receptor (EGFr) in normal oral mucosa and in 12 oral papillomas in which the presence of Human Papilloma Viruses (HPV) had been ascertained through in situ hybridization. The study reveals that in normal oral mucosa EGFr is usually expressed in basal cell layers whereas in oral papillomas EGFr is detectable throughout the whole thickness of the lesions. Furthermore, when HPV type 6 is present (10 cases) in the lesion, the pattern of expression of EGFr is almost exclusively membranous whereas in two HPV type 16-induced papillomas the reaction product with monoclonal anti-EGFr Antibodies appears confined to the intracytoplasmic paranuclear area. The present investigation, therefore, seems to show a peculiar correlation between HPV infection and EGFr immunoreactivity in papillomas of the oral mucosa. The pattern of immunoreactivity appears to be related to the specific type of HPV detectable in the lesion and it may possibly depend on the interactions between host and viral genomes. Those interactions might be different for HPV 6 and HPV 16 and may consequently lead to divergent expression of EGFr.