Background: MMR-D, characterized by loss of protein expression of MMR protein(s) (MLH1, MSH2, MSH6, PMS2) by immunohistochemistry (IHC) occurs in 20-25% of ECs & serves as a screening test for Lynch Syndrome (LS). MMR-D may be somatic, characterized by MLH1/PMS2 protein loss & presence of MLH1 promoter hypermethylation (MLH1-HM+) or may result from a germline mutation in a MMR gene (LS). However, a proportion of MMR-D EC patients (pts) have absence of an identifiable germline alteration & absence of MLH1-HM and are referred to as having “Lynch-like syndrome” (LLS). Clinical & family history (hx) of LLS in EC remains poorly characterized. Methods: Database review identified all MMR-D EC pts who were evaluated at MSKCC 2007-2015. Electronic medical records & progeny pedigrees were reviewed. Statistics performed via GraphPad Prism v. 6, Mann Whitney U compared median age, Fishers exact test was performed on remaining variables. Results: Of 226 MMR-D EC cases, 101 (45%) had MLH1/PMS2 loss with MLH1-HM+, 69 (31%) had LS & 56 (25%) LLS. IHC in LS pts demonstrated loss of: MSH2/MSH6, 36 (52%); MLH1/PMS2, 14 (20%); PMS2, 8 (12%); MSH6, 11 (16%) & in LLS pts: MSH2/MSH6, 23 (41%); MLH1/PMS2, 8 (14%); PMS2, 4 (7%); MSH6, 21 (38%). Germline mutations in LS pts included: MLH1, 14 (20%); MSH2, 33 (48%); MSH6, 16 (23%); PMS2, 9 (13%). Patient & family hx characteristics of LS & LLS pts are provided in the table. Conclusions: The majority of LLS EC pts have IHC MSH2/MSH6 or MSH6 loss & appear to have a weaker personal & family cancer hx compared with LS EC pts. The biology & clinical implications of MMR-D in this group is unknown & somatic mutational profiling is being undertaken to explore alternative mechanisms for MMR-D, results will be presented.