Recent technological advances in large-scale sequencing resulted in the identification of common genetic alterations in HNSCC, including mutations occurring in genes of the phosphoinositide 3-kinase (PI3K) pathway [1–5], as PIK3CA, GRB1, PIP5K3, AKT2, TSC1, TSC2, mTOR, Rictor, Raptor among others. This evidence concerns the gene PIK3CA and head and neck squamous cell carcinoma.