About 3% of men in developed countries die from prostate cancer. No conclusive evidence, however, either supports or refutes the benefit of prostate-cancer screening. More than 200000 participants are needed for a screening study with prostate-cancer-specific death as the endpoint. A relative reduction in prostate-cancer mortality of 25% leads to a decrease in absolute risk of less than 1%—a difference of 75 individuals between the control and screening group. Participant non-compliance and small inaccuracies in attributing cause of death need to be compensated for in study size, requiring several million participants. Screening trials with insufficient sample sizes might show a lowering of cancer-specific mortality but not detect increases in all-cause mortality related to screening. Studies of a manageable size have too little discriminatory power and last a long time. Furthermore, results become available decades after trial initiation, by which time they are probably antiquated. Whether screening for prostate cancer is beneficial cannot be assessed in trials, a statement that might also be true for other diseases with low specific mortality.