In this report, we review the critical issues concerning the early detection of prostate cancer in patients presenting with symptoms of benign prostatic hyperplasia (BPH). Only with the recent introduction of serum prostate-specific antigen (PSA) testing and transrectal ultrasonography (TRUS)-guided biopsy has the question arisen to what extent the treating physician has a responsibility to rule out prostate cancer before recommending treatment-or watchful waiting-for men with clinical BPH. Uneasiness and uncertainty also result from the development of alternative therapies that do not provide tissue for pathological analysis, or alter serum PSA levels in a poorly predictable fashion. Current early detection strategies, in this clinical situation, pose unique problems, largely because of the great degree of overlap in serum PSA among men with localized prostate cancer and BPH. The underlying goal is to distinguish patients with BPH alone from those with clinically significant, but organ-confined and potentially curable prostate cancer. Treatment for prostate cancer may take precedence over BPH management strategies, while at the same time address the symptoms associated with coexistent clinical BPH. The issues discussed in this report should aid the clinician in the evaluation of patients with clinical BPH. Further studies are clearly needed that may ultimately enhance our ability to discriminate patients with clinically significant organ-confined prostate tumors from those with BPH alone.