Cancer is the second leading cause of death in New York City, with nearly 15,000 deaths each year. The urban setting of New York City provides ready access to large and diverse populations for whom racial/ethnic disparities in cancer risk and outcomes can be examined. A new cohort study was undertaken with several aims: (1) to provide a database and biorepository for studies of cancer etiology and pathogenesis, including host genetics; (2) to differentiate risk factors that contribute to racial/ethnic disparities in cancer risk, prevention, control, incidence, mortality, and survival; (3) to provide timely data on cancer risk and preventive behaviors that can be used to mobilize and then evaluate public health programs. Scientists from multiple institutions contributed to protocol design and implementation. Study instruments included demographics, personal and family history of cancer, risk and prevention efforts. End points include linkage with registries and medical record reviews. Using venue-based sampling with quotas, 18,187 adults aged 30 years or older were recruited over a year to undergo a baseline questionnaire, venipuncture, and contact information. The sample was 39% male, 37% older than 50 years, 58% white, 20% African American, 18% Hispanic, and 9% Asian. In terms of family history of cancer, 21% reported mother, 21% reported father, and 5.9% reported both parents with cancer; 8.5% reported any sibling with cancer. At baseline, 1,231 participants reported prior cancer. Showing the feasibility of constructing a cohort based in New York City, plans proceed for additional recruitment and analyses on the salient questions about cancer.