Abstract: Objective: To determine the prognostic value of quantitating protein expression of the HGF receptor c- Met in patients with oropharyngeal cancer. Methods: A new system of automatic quantitative analysis for protein expression was used to study the levels and pattern of expression of c-Met protein in a tissue microarray composed of 108 oropharyngeal carcinoma cases. Results: Compared to those with light staining, there was an increased local recurrence rate (77% versus 37%), a decreased 5- year disease- free survival time (8% versus 33%) and a significantly reduced overall survival rate(8% versus 35%) in the samples from patients with high nuclear c- Met levels. In a multivariate Cox regression analysis, intranuclear c- Met expression was the most significant prognostic factor, independent of local recurrence, disease- free survival time or the overall survival time. However, cytoplasmic c- Met expression was not associated with prognosis. Cytoplasmic c- Met expression was closely correlated with MAPK expression (P<0.001) but not with nuclear c- Met expression. Conclusion: Intranuclear c- Met expression is related to a poor prognosis for patients with oropharyngeal cancer. Expression of c- Met may be caused by activation of alternative pathways in aggressive tumors.