Background: CD147 is upregulated in multiple cancer types, but its expression in advanced cutaneous squamous cell carcinoma (SCC) is unknown. Our purpose was to evaluate the expression patterns of CD147 and related monocarboxylate transporters (MCT1, MCT4) to determine their correlation with survival. Methods: This is a retrospective cohort study of patients with advanced stage cutaneous SCC of the head and neck who presented to a tertiary care center between 1998 and 2006 (n=50). CD147, MCT1 and MCT4 expression levels were assessed using immunofluorescence analysis of archived tumor samples and correlated with survival and clinicopathologic characteristics. Results: The majority of patients (92%, n = 46) were diagnosed with stage III disease, with 46% (n = 23) having positive regional lymph node metastasis and 8% (n = 4) with distant metastasis. Primary malignancies had an overexpression of CD147 (78%; n = 35), MCT1 (23%; n = 10) and MCT4 (47%; n = 20). In addition, there was a significant relationship between the overexpression of CD147 and node positive disease (p = 0.048). Two- and five-year survival rates were 69 and 61%, respectively. There was a trend toward decreased survival in patients with overexpression of CD147 (p = 0.17), MCT1 (p = 0.11) and MCT4 (p = 0.15). Conclusion: CD147 may represent a biomarker or potential therapeutic target in advanced cutaneous SCC. Copyright © 2012 John Wiley & Sons A/S.