Background The significance of epidermal growth factor receptor (EGFR) expression in advanced cutaneous squamous cell carcinoma (SCC) of the head and neck remains poorly understood. Methods We performed a retrospective review of patients with advanced-stage (stage III or stage IV) cutaneous SCC of the head and neck (n = 56). Results The majority of patients (91%) had stage III disease, with 54% having regional metastasis and 9% with distant metastasis. Two-year survival was 64% and the 5-year survival was 56%. EGFR was found to be overexpressed in 56% of primary tumors and 58% of regional metastatic disease. Overall survival did not correlate with EGFR (p =.47) expression in primary lesions, nor was it associated with an increase in regional (p =.74) or distant metastasis (p =.56). Furthermore, there was no correlation between clinicopathologic characteristics and EGFR expression Conclusions These data do not suggest upregulation of EGFR is associated with poor survival or aggressive disease. © 2011 Wiley Periodicals, Inc.