Cancer screening programs aim at reducing the tumor-related morbidity and mortality by early detection of malignant tumors or precancerous lesions. The basic ethical dilemma in cancer screening is, however, that many people have to be exposed to the burdens and risks of the intervention for a few people to benefit from early cancer diagnosis. This article discusses under which conditions it is ethically acceptable to offer or even recommend cancer screening. First, the benefit of the program in terms of a reduced cancer-related mortality should be proven by randomized controlled trials. The risks and burdens of the program related to the side effects of the investigation itself, false-positive findings, as well as overdiagnoses and overtherapy should be in an acceptable relationship to the expected benefit of the program. In addition to a solid empirical scientific basis, the benefit-harm evaluation necessarily involves value judgments. The potential participants in the screening program therefore should receive transparent, objective, unbiased, and understandable information to enable them to make a truly informed choice about participation. Given the complex benefit-risk assessment, it is discussed whether-and if so under which circumstances-it is ethically acceptable to make a recommendation for or against participation in a cancer screening program. Socioempirical research, such as focus group studies and public deliberations, can be used to elicit the preferences and value judgments of members of the target population that should be taken into consideration in recommendations about a cancer screening program.