BACKGROUND. Few research studies have been conducted on cancer prevention and control at the workplace. This article presents an overview of the largest worksite cancer control trial in the United States--The Working Well Trial--conducted in 114 worksites by four study centers, a coordinating center, and the National Cancer Institute. The trial's organizational structure, research design, dependent measures, and theoretical model for intervention are described. Special features of the trial include using the worksite as the unit of randomization, intervention, and evaluation and a theory-driven conceptual model of intervention that places emphasis on individual and organizational targets for change, uses the transtheoretical stage of change model to guide a sustained 2-year multiple risk factor intervention, and makes use of volunteer resources within the worksite to reduce cost, increase participation, and improve tailoring to individual needs. The trial will have a potential impact on over 25,000 workers. CONCLUSION. The issues raised in this overview have implications for the evaluation and dissemination of cancer prevention and control programs to defined populations.