The mission of Case Comprehensive Cancer Center (Case CCC), now in its 25th year of NCI designation, is to promote a coordinated, translational research-oriented culture of scientific discovery applied to human cancers, with dissemination to patients and populations to improve cancer prevention, detection, treatment, cure, and survivorship. The Center provides leadership and oversight of collaboration for basic cancer research oriented toward identification of novel therapeutic targets; prevention, control and population research; therapeutic and non-therapeutic clinical research across the disease spectrum; and community outreach. The Center coordinates all aspects of cancer research in Cleveland and Northern Ohio, including activities of the affiliate institutions of Case Western Reserve University School of Medicine: Cleveland Clinic and University Hospitals. The Center provides opportunities to participate in clinical trials to almost 10,000 cancer patients who are newly diagnosed annually in the region. The opening in 2010 of the new freestanding cancer hospital, UH Seidman Cancer Center, and the funding of the GI SPORE represent major achievements in this past grant cycle. The Case CCC is organized around 8 Scientific Programs, 15 shared resources, and a clinical and behavioral cancer research infrastructure that prioritizes innovative translational research and investigator-initiated clinical trials that cut across the Scientific Programs. The Case CCC includes 232 full members (335 total members) from 5 schools and 30 academic departments who actively participate in Cancer Center activities including Program and Core meetings and retreats, leadership committees, and scientific focus groups, each promoting a transdisciplinary approach that facilitates discovery and clinical application. The Cancer focus of the Center is exceptional, with over $116l\/l in total funding and over $45M in total NCI funding. Institutional commitment is also exceptional with over $115M dedicated to cancer research in the next cycle and over $350M in construction anticipated. The Case CCC and its affiliate institutions have established an outstanding infrastructure that enables its members to improve the prevention, diagnosis, and treatment of cancer through discovery, implementation and dissemination, while providing state-of-the-art care and treatment to cancer patients and their families. The Case CCC is a significant partner with the NCI in its effort to change the practice of cancer care through discovery and clinical research of the highest quality.