Cancer screening may be offered to a population opportunistically, as part of an organized program, or as some combination of the preceding two options. Organized screening is distinguished from opportunistic screening primarily on the basis of how invitations to screening are extended. In organized screening, invitations are issued from centralized population registers. In opportunistic screening, however, due to the lack of central registers, invitations to screening depend on the individual's decision or on encounters with health care providers. The current article outlines key differences between organized and opportunistic screening. In the current study, literature searches were performed using PubMed and MEDLINE. Additional data were assembled from interviews with health officials in the five countries investigated and from the authors' personal files. Opportunistic screening was found to be distinguishable from organized screening on the basis of whether screening invitations were issued from centralized population registers. Organized screening programs also assumed centralized responsibility for other key elements of screening, such as eligibility requirements, quality assurance, follow-up, and evaluation. Organized programs focused on reducing mortality and morbidity at the level of the population rather than at the level of the individual. Thus, programs did not necessarily offer the most sensitive screening test for a particular cancer, and tests sometimes were offered at suboptimal intervals with respect to individual-level protection. Nonetheless, organized systems paid greater attention to the quality of screening, as measured by factors such as cancer detection rates, tumor characteristics, and false-positive biopsy rates. As a result, participants in organized screening programs received greater protection from the harmful effects associated with screening. In addition, organized programs worked more systematically toward providing value for money in an inevitably resource-limited environment. Although organized and opportunistic models of screening can yield similar uptake rates, organized programs exhibited greater potential ability to reduce cancer incidence and mortality, because of the higher levels of population coverage and centralized commitment to quality and monitoring; were more likely to be cost-effective; and offered greater protection against the harmful effects associated with poor quality or overly frequent screening. Cancer 2004. © 2004 American Cancer Society.