This prompted us to perform a thorough analysis of PI3K/AKT/mTOR pathway components to investigate the mutational status of PIK3CA and AKT1 genes and the immunohistochemical expression of a number of pathway-related proteins (EGFR, PDK1, p-AKT, PTEN, p-S6) using a consecutive series of 93 surgically treated HNSCC patients, and to establish correlations with the clinicopathological parameters and disease outcome. This evidence concerns the gene PDK1 and head and neck squamous cell carcinoma.