Altered cadherin expression is important for metastasis in many carcinomas including head and neck squamous cell carcinoma (SCC). We evaluated E- and N-cadherin expression specifically in oropharyngeal SCC and correlated this with clinical and pathologic features. Oropharyngeal SCC patients with clinical follow up information were identified from clinician databases from 1996 through 2007 and tissue microarrays created. Tumors had been previously typed histopathologically as keratinizing, non-keratinizing, or non-keratinizing with maturation, and had known p16 and human papillomavirus status, respectively. Immunohistochemistry was performed on the microarrays, and staining was evaluated for presence and intensity (0 = negative, 1 = weak, 2 = moderate, 3 = strong) both visually and also with digital image analysis software. Of 154 cases, E-cadherin was expressed in 152 (98.7%) and N-cadherin in 17 (11.5%). Neither E- nor N-cadherin expression was statistically significantly associated with histopathologic type (P = 0.082 and P = 0.228, respectively). E-cadherin staining intensity was not statistically significantly associated with nodal or distant metastasis, either visually or by image analysis, (P = 0.098 and P = 0.963 respectively) nor was N-cadherin (P = 0.228 and P = 0.935 respectively). Neither E- nor N-cadherin expression was associated with death from disease (P = 0.995; P = 0.964, respectively). E-cadherin is extensively expressed by oropharyngeal SCC, even the non-keratinizing type. Our results suggest that cadherin expression may not be a predictor for nodal or distant metastasis in these tumors. Mechanisms independent of cadherin expression may be important for metastases in oropharyngeal SCC.