Even though more than 90% of HNCs overexpress EGFR (the expression progressively increases according to the histological malignant transformation, from hyperplasia to invasive carcinoma), which is associated with high local recurrence rate and poor survival, only a modest subgroup of HNCs shows amplified copy numbers or mutational activation of the EGFR gene, suggesting the existence of other mechanisms acting downstream on the pathways [123]. This evidence concerns the gene EGFR and invasive carcinoma.