Abstract The National Cancer Institute (NCI) is developing a Patient-Derived Models Repository (PDMR) comprised of quality-controlled early-passage clinically-annotated patient-derived xenografts (PDXs) and in vitro patient-derived cell cultures (PDCs), including tumor cell and cancer-associated fibroblast cell cultures, to serve as a resource for public-private partnerships and for academic drug discovery efforts. These PDMs will be clinically-annotated with molecular information (whole exome sequence, RNASeq) available in a publicly accessible database and will be available to the extramural community for research use. The PDMR was established by NCI at the Frederick National Laboratory for Cancer Research (FNLCR) in direct response to discussions with academia and industry; the oncology community’s highest priority need is better preclinical models that more faithfully reflect the patient’s tumor and are associated with the patient’s treatment history. NCI has focused on collecting specimens from patients with cancer that are under-represented in many other PDX collections such as head and neck, pancreatic, bladder, ovarian and small cell lung cancers, melanomas and sarcomas. In addition, NCI is increasing its focus on creating PDXs from minority/underserved populations and will soon be expanding to include pediatric cancers. The PDMR generates the majority of its PDXs by subcutaneous implantation; however certain histologies have better take-rates in either orthotopic or alternate implant sites. All SOPs and quality-control standards developed by the PDMR as well as those shared by collaborators will be posted to the public web site that houses the PDMR database. The overall goal of NCI is to create a long-term home for at least 1000 models such that sufficient biological and clinical diversity is represented to allow researchers to ask questions such as: what is the impact of tumor heterogeneity on target qualification or clinical response; do PDXs more faithfully represent the human tumor for pharmacodynamic assay and predictive marker development; or can an adequately powered preclinical PDX clinical trial lead to better evaluation of therapies for future clinical use? Grant Support: This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Citation Format: Yvonne A. Evrard, Michelle Ahalt-Gottholm, Sergio Alcoser, Carrie Bonomi, Suzanne Borgel, John Carter, Biswajit Das, Vivekananda Datta, Cheryl Davis, Kelly Dougherty, Michelle Eugeni, Marion Gibson, Catherine Karangwa, Jason Lih, Dianne Newton, Han Si, Shivaani Kummar, Larry Rubinstein, Alice Chen, P. Mickey Williams, Melinda G. Hollingshead, James H. Doroshow. The National Cancer Institute’s patient-derived models repository (PDMR) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3840. doi:10.1158/1538-7445.AM2017-3840