In vitro, we observed that trastuzumab synergizes with cetuximab at the cellular level in HER2+ EGFR+ HNSCC and, by modulating the dose of trastuzumab, we identified that this synergy is primarily driven by HER2 inhibition, although further study of synergistic interactions between IC25 and IC50 should be investigated. This evidence concerns the gene EGFR and head and neck squamous cell carcinoma.