The phosphoinositide 3-kinase/protein kinase B/ mammalian target of rapamycin (PI3K/Akt/mTOR) pathway shows a high frequency of mutation in HNSCC with up to 62% of cases carrying activating genetic changes in PI3K in both HNSCC entities [7,8,9]. The gene discussed is AKT1; the disease is head and neck squamous cell carcinoma.