Cancer screening is an important component of prevention and early detection in public health and clinical medicine. The evidence for cancer screening, however, is often contentious. A description and explanation of disagreements over the evidence for cervical, breast, and prostate screening may assist physicians, policymakers, and citizens faced with screening decisions and suggest directions for future screening research. There are particular issues to be aware of in the evidence base for each form of screening, which are summarized in this paper. Five tensions explain existing conflicts over the evidence: (1) data from differing contexts may not be comparable; (2) screening technologies affect evidence quality, and thus evidence must evolve with changing technologies; (3) the quality of evidence of benefit varies, and the implications are contested; (4) evidence about harm is relatively new, there are gaps in that evidence, and there is disagreement over what it means; and (5) evidence about outcomes is often poorly communicated. The following principles will assist people to evaluate and use the evidence: (1) attend closely to transferability; (2) consider the influence of technologies on the evidence base; (3) query the design of meta-analyses; (4) ensure harms are defined and measured; and (5) improve risk communication practices. More fundamentally, there is a need to question the purpose of cancer screening and the values that inform that purpose, recognizing that different stakeholders may value different things. If implemented, these strategies will improve the production and interpretation of the methodologically challenging and always-growing evidence for and against cancer screening.