The PTEN hamartoma tumor syndrome (PHTS) includes not only the entity Cowden syndrome (CS, MIM 158350) which is the focus of this chapter, but also Bannayan-Riley-

Ruvalcaba syndrome (BRRS, MIM 153480), Proteus syndrome (PS, MIM 176920), and

Proteus-like syndrome (PSL) (1). Disorders in this heterogeneous group are all, to varying

degrees, associated with germline mutations of the PTEN tumor suppressor, localized to 10q23.2 (2,3). PTEN is a dual-specificity phosphatase, having both phospholipid and

protein phosphatase activities (4-6). PTEN plays a crucial role in controlling cell growth,

cell spreading, and mediating apoptosis and cell cycle arrest.