Several recent advances have been made in our understanding of the pathogenesis of endometrial tumours, particularly endometrioid endometrial carcinoma (EEC). Mutations in thePTENgene and microsatellite instability (MSI) are common genetic abnormalities in EECs, and distinguish these lesions from other histological subtypes of endometrial carcinoma. Endometrial precancers are monoclonal lesions that share a common genetic lineage with invasive EEC, includingPTENmutations and MSI. Mutations of thePTENtumour suppressor gene have been identified in histologically normal-appearing endometrium exposed to oestrogen, 18-55% of endometrial precancers and 26-80% of EECs.PTENhas been shown to play several roles in tumour suppression, including cell cycle arrest and promotion of apoptosis. Loss ofPTENfunction predisposes endometrial cells to neoplastic transformation, particularly in high-oestrogenic states. MSI is another common alteration seen in EECs and endometrial precancers, and some studies have reported an association between MSI andPTENmutations. The replication error that results in MSI may facilitate the development ofPTENmutations in some, but not all, cases of EEC. The prognostic significance ofPTENgene mutations and MSI in endometrial carcinoma is controversial. Further study is needed to delineate the different pathogenetic pathways of EEC and their natural history.