The National Cancer Institute (NCI) established the AIDS and Cancer Specimen Resource (ACSR) in 1994 to support the collection and expert preservation of clinically-annotated biospecimens for multidisciplinary research, bridging laboratory basic science with clinical, behavioral, and epidemiological studies. For the past 19 years, the ACSR has provided the foundation for successful translational research reliant on consistent access to high-quality well-annotated biospecimens. It has accomplished this via development of extensive expertise in methods for specimen collection and maintenance including specimen stability and full functionality overtime. The ACSR remains crucial to HIV-translational research, expanding services to researchers, and instituting practices to complement innovative new experimental directions by global HIV investigators. Since 2008, the current grant cycle, ACSR banked over 50,000 and distributed over 10,000 biospecimens to scientists worldwide. ACSR has also developed unique programs, offering project consultation and researcher training at all levels that assist with specimen choice and inform about biorepository procedures, thus ensuring appropriate handling and use of valuable biospecimens for research. The work accomplished under the current ACSR will be leveraged and transitioned to achieve the Specific Aims for the new ACSR to: 1) develop and maintain the ACSR infrastructure that allows efficient translation of the overall ACSR mission (to support current and future trends in HIV/AIDS malignancy research) to an ongoing functional program 2) provide scientific leadership, expand utilization and relevance of the resource; 3) acquire, maintain and distribute a diverse collection of high-quality and well-annotated biospecimens and; 4) support initiatives, projects, programs and collections, both national and international through ACSR services. To accomplish these aims we will restructure the current ACSR to a single multisite ACSR, under the direction of the Office of the Chairs (OC) and administered by the Central Operations and Data Coordinating Center (CODCC) to be led by senior investigators in a shared leadership role, Drs. Michael McGrath and Sylvia Silver, representing the continuing UCSF and George Washington University (GW) Regional Biospecimen Repositories (RBR). The two original RBRs, UCSF and GW, account for > 80% of the overall ACSR inventory (500,000+ specimens) and for supplying 90% of the specimens disbursed to researchers in the past five years. The proposed ACSR also will add value through transitioning affiliate programs at the University of Arizona, Tucson, and Baylor College of Medicine to new RBRs. The ACSR will continue to evolve and streamline operations to incorporate a state of the art inventory system, and new technologies and methods to improve specimen viability. The ACSR is a dynamic entity that has used innovative and novel approaches to meet changes in the epidemic and research directions, and is well positioned to continue support of current and future trends in HIV research that will have a positive impact on diagnosis and management of HIV-malignancies worldwide.