Overexpression of c-erbB-2 (also known as HER-2/neu) has been found in many human cancers, including head and neck squamous cell carcinoma (SCC). We therefore examined expression of the oncoprotein in oral SCC primary tumor samples and compared its relationship with clinical stages and survival rate. Out of 80 cases of oral SCC, high expression level (++ or +++) of c-erbB-2 was found in 41 cases. Of the 80 cases with follow-up information, 39 were further investigated for the correlation of expression level of c-erbB-2 and survival rate. Overexpression of the oncoprotein was significantly correlated with shorter overall survival, and the patients with low and no expression of c-erbB-2 had much higher survival rates. Overexpression of c-erbB-2 was also significantly correlated with nodal stage and metastasis. We found that high expression level of c-erbB-2 was frequently detected in oral cancer cell lines but not in the other head and neck SCC cell lines. Thus, we conclude that overexpression of c-erbB-2 is a frequent event in oral SCC and is correlated with poor survival and may be used as a poor prognostic factor.