Screening for cancer in children is uncommon. However, in children with congenital syndromes associated with Wilms' tumor, conditions exist that potentially make screening effective. This select population of children 1) are relatively easily identified; 2) have a high incidence of Wilms' tumor; 3) if identified before development of Wilms' tumor, may have a decrement in morbidity/mortality; and 4) are amenable to a simple and acceptable screening technology, renal sonography exams. Many clinicians have recommended screening for cancer in children with congenital syndromes associated with Wilms' tumor. However, neither costs nor effectiveness of such recommendations have been evaluated systematically. The strongest evidence for or against Wilms' tumor screening in this select population would be provided by a randomized screening trial. Prior to undertaking such a trial, the key parameters that dominate the cost and effectiveness of screening should be identified. Simulation models, such as cost effectiveness analysis, offer a starting point for deciding whether cancer screening is appropriate, and if so, under what set of conditions. We review basic conditions required for a successful screening trial in children with syndromes that are at increased risk of Wilms' tumor. We also discuss the use of cost-effectiveness analysis as a preliminary step in determining the feasibility of an intervention trial.