Not only the controversial in vivo and in vitro results with mTOR inhibitors demonstrate the difficulties to predict outcome to mTor inhibitors, but also the heterogeneously altered components of the mTOR pathway in tumor cells impact functionality of mTOR signaling, starting with the frequently reduced levels/mutations of the tumor suppressor gene PTEN or mutations/amplifications of Phosphoinositide 3-kinase (PI3K). The gene discussed is PTEN; the disease is neoplasm.