The tumor suppressor gene PTEN (phosphatase and tensin homolog deleted on chromosome ten), often referred to as MMAC1 (mutated in multiple advanced cancers 1), is located on 10q23.31 and encodes a 47 kDa dual-specificity phosphatase that has both lipid and protein phosphatase activity. Its inactivation results in constitutive activation of the PI3K/AKT pathway and in subsequent increase in protein synthesis, cell cycle progression, migration, and survival. Deletions affecting the long arm of chromosome 10 have been detected in 30 to 50% of early and advanced stage sporadic melanomas and about 40 to 70% of prostate cancers. In both tumor entities loss of PTEN has been associated with poor clinical outcome. Currently, several drugs targeting the PI3K/AKT pathway for the therapy of solid tumors have entered clinical trials.