 Results of genetic research can today help to diagnose most of the segmental overgrowth syndromes which means they can clearly be named. Genes of the PI3KAKTPTENmTOR signalling pathway have been identified to be causative for some of these syndromes. PTEN germline mutations have been known to be present in SOLAMEN, Cowden and Ruvalcaba syndrome patients all showing tissue overgrowth and close clinical overlap. However, very rarely, somatic PTEN mutations could be detected in surgical specimen of lipomas or hamartomas of other segmental overgrowth patients. Only recently, recurrent somatic activating mutations of AKT1 have been identified in overgrowth tissue of Proteus syndrome patients. Because AKT1 is also activated by loss-of-function mutations in PTEN, patients with syndromes harbouring germline PTEN mutations SOLAMEN, Cowden and Ruvalcaba and Proteus syndrome patients with activating mutations of AKT1 show close overlap in clinical manifestations. Furthermore, somatic PI3KCA mutations have been described to be responsible for the CLOVE syndrome, again a phenotypically closely related variant of the other overgrowth syndromes. These genetic results confirmed that patients with overgrowth all share a common feature involving the PI3KAKTPTENmTOR signal pathway. 