In 2006, the anti-EGFR monoclonal antibody (mAb) cetuximab, was approved by the Food and Drug Administration (FDA) in combination with radiotherapy for locoregionally advanced HNSCC (median overall survival (OS) of 4.1 years versus 2.4 years with radiotherapy alone) and in combination with platinum-based therapy and infusional 5-fluorouracil (EXTREME regimen) for the first-line treatment of patients with recurrent/metastatic (R/M) HNSCC (median OS 10.1 months versus 7.4 months with chemotherapy alone) (5–7). The gene discussed is EGFR; the disease is head and neck squamous cell carcinoma.