The exact role of oncogenes and proto-oncogenes in the development of squamous cell carcinoma of the head and neck (SCCHN) is still debatable. The expression of the c-erbB-2, c-erbB-3 and c-erbB-4 members of the epidermal growth factor receptor family was examined in 16 fresh frozen tissue specimens of SCCHN using avidin-biotin complex immunohistochemistry, with monoclonal and/or polyclonal antibodies directed against each. Eight fresh frozen tissue specimens of normal oral mucosa were included as controls. Of the SCCHN examined, mixed membrane/cytoplasmic staining (moderate to intense) of c-erbB-2 was found in 14/16 cases (88%). When present in the specimen, immunopositive staining of c-erbB-2 was seen in some of the oral surface epithelial cell layers (basal, intermediate and/or superficial) as well as the tumour islands. Weak cytoplasmic staining of c-erbB-3 and c-erbB-4 was found in 13/16 (81%) and 11/16 (69%) cases respectively. When present in the specimen, c-erbB-3 and cerbB-4 immunopositive staining was seen in some of the oral surface epithelial cell layers (basal, intermediate and/or superficial) as well as the tumour islands. For the positive carcinomas for c-erbB-2, c-erbB-3 and c-erbB-4, the epithelium located near the carcinomas showed weak mixed membrane/cytoplasmic staining of c-erbB-2 in 5/14 cases (36%), weak cytoplasmic staining of c-erbB-3 in 7/13 cases (54%) and of c-erbB-4 in 3/11 cases (27%). All the normal control oral mucosa showed the same pattern of staining for c-erbB-2, c-erbB-3 and c-erbB-4 found in the epithelium located near the carcinomas. Only expression of c-erbB-2 was found to correlate with the increase in the tumour stage, while co-expression of c-erbB-2, c-erbB-3 and c-erbB-4 was found to correlate with the patient survival time in 25% of the carcinomas examined. The present study shows that a) expression of c-erbB-2, but not c-erbB-3 and c-erbB-4 correlates with the increase of the tumour stage b) co-expression of c-erbB-2, c-erbB-3 and c-erbB4 correlates with decreased survival time in some of the cases of SCCHN, but not the majority c) co-expression of the c-erbB family in normal oral mucosa as well as in the carcinoma may question whether the increased tendency for development of the disease is due to co-expression of c-erbB proto-oncogenes in head and neck lesions.