Objective: To describe the factors critical to implementation of a nurse-based system to increase access for American Indian women to breast and cervical cancer screening. Material and Methods: We report the experience of 103 nurses at 40 clinics who were trained to use the nurse-based screening system. In addition, the critical elements are discussed in the context of one particularly successful site. Results: Fifteen factors were identified as critical to the implementation of a nurse-based cancer screening process once a nurse had been trained to perform clinical breast examinations and collect Papanicolaou (Pap) test specimens: knowledge of benefit, skills, organization, adequate return, perceived patient demand, perceived effectiveness, legitimacy, confidence, commitment, adequate resources, a data-driven iterative approach to program implementation, an objective measure of quality, leadership, the passage of time, and a focus on delivering the service to the patient. For example, in one site that was particularly successful, the nurses, administrators, and other key health- care professionals contributed their respective resources to implement the screening program. The program was also supported by the lay community, the state board of nursing, and the state health department breast and cervical cancer control program. During the 3-year study period, the 103 nurses performed screening tests on 2,483 women, and only 18 of the Pap test specimens were unsatisfactory. Conclusion: Nurse-based systems designed to collect high-quality Pap test specimens and perform detailed clinical breast examinations can be implemented if the factors that are critical to implementation are identified and addressed.