PTEN (Phosphatase and tensin homolog) is a dual-specificity protein phosphatase, dephosphorylating tyrosine-, threonine- and serine-phosphorylated proteins. PTEN has also a lipid phosphatase activity that is critical for its tumor suppression function. PTEN antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival. Defects in PTEN are the cause of numerous cancers such as in Cowden disease (breast, thyroid and skin cancer predisposition), Lhermitte-Duclos disease, and head and neck squamous cell carcinoma.