The high prevalence of unsuspected prostate cancer among middle-aged and elderly men is unique among cancers. With their uncertain natural history, unsuspected prostate cancer cases may be misclassified into control groups in which they can obscure the identification of prostate cancer risk factors in case-control studies. Assuming that the exposure experience of diagnosed and of unsuspected prostate cancers is the same (nondifferential misclassification), case-control odds ratios are biased toward the null, which may provide a rationale for reexamining findings in negative case-control studies of prostate cancer. This article reviews the evidence supporting a high prevalence of prostate cancer and describes formulae that can be used to adjust for misclassification bias in completed case-control studies and to estimate required sample sizes in proposed studies.