Our systematic review and meta-analysis on the prognostic implications of EGFR overexpression in oral cancer, conducted on 50 studies and 4631 patients, points out that there is an association with lower overall survival (HR = 1.38, 95%CI = 1.06–1.79, p = 0.02), higher probability of developing neck lymph node metastases (OR = 1.37, 95%CI = 1.01–1.86, p = 0.04), and higher risk of developing poorly differentiated tumors (OR = 1.43, 95% CI = 1.05–1.94, p = 0.02). This evidence concerns the gene EGFR and lip and oral cavity carcinoma.