Despite numerous studies evaluating second-opinion surgical programs, we are unaware of work evaluating the cost effectiveness of a second opinion for pathology prior to surgery. One of six pathologists reviewed the pathology of the outside needle biopsies of 535 consecutive men referred to Johns Hopkins Hospital for radical prostatectomy over a 12-month period (from October 1993 until October 1994) before the men underwent surgery. Of the 535 needle biopsies initially diagnosed on the outside as adenocarcinoma of the prostate, seven (1.3%) were reclassified as benign upon pathology review at Johns Hopkins Hospital. The most common lesion misinterpreted as adenocarcinoma was adenosis or less pronounced examples of adenosis consisting of foci of crowded glands (five cases). Foci of atrophy in the remaining two cases were misdiagnosed as adenocarcinoma of the prostate. Upon subsequent clinical work up, six of seven men were considered not to have adenocarcinoma, and their surgery was cancelled. The cost for reviewing all 535 preoperative needle biopsies was $44,883, which included the cost of immunohistochemical studies for high-molecular-weight cytokeratin and repeat biopsies and ultrasounds in men whose diagnoses were reversed. The total cost of the radical prostatectomies had the six men undergone surgery was estimated at $85,686, including hospitalization, anesthesia, radical prostatectomy pathology, and surgery. This cost savings did not include other costs resulting from lost wages, morbidity, or potential litigation. Second-opinion pathological evaluation of prostate biopsy before radical prostatectomy is cost effective and has a major impact on clinical treatment for a subset of patients.