The objective of this study was to determine the expression of the c-erB-2 oncoprotein via immunohistochemistry of archival clinically localized human prostate cancers and to compare these results to known clinical prognostic factors. In addition, positive staining cases were subjected to differential polymerase chain reaction to assess for c-erbB-2 gene amplification. Immunohistochemical staining with a polyclonal antibody (pAb 1) was performed on archival radical prostatectomy specimens. To standardize the staining, positive and negative control material was generated using c-erbB-2 transfected NIH3T3 cells grown on agar plugs, formalin fixed, paraffin embedded and processed on glass slides for immunohistochemistry. Definite positive membranous staining was detected in 18 of 53 neoplastic cases (34%). In addition, 9 cases of benign prostatic hyperplasia were stained without evidence of c-erbB-2 expression detected. Either focal or diffuse membranous staining was identified in 6 of 27 (22%) well, 8 of 20 (40%) moderately and 4 of 6 (66%) poorly differentiated tumors (p = 0.03, chi-square test for trend). Positive staining occurred in 6 of 18 patients (33%) with pathological stage B and 12 of 33 (36%) with pathological stage C disease. At a mean of 36 months, complete followup was available for 16 of the 18 positive cases and 30 of the 35 negative cases. For stage B 1 of 6 positive (16.7%) versus 1 of 12 negative (8%) staining cases showed progression (p = 1.0). For stage C 7 of 12 positive (58.3%) versus 9 of 21 negative (42.9%) cases showed progression (p = 0.48). Deoxyribonucleic acid was extracted from the exact same archival paraffin blocks for the c-erbB-2 protein positive cases and subjected to differential polymerase chain reaction analysis, which revealed no c-erbB-2 gene amplification. This study demonstrates that approximately a third of all clinically localized prostate cancers express the c-erbB-2 oncoprotein via immunohistochemistry using pAb-1 on archival material, c-erbB-2 oncoprotein expression does not appear to be a prognostic marker for prostate cancer although our results are preliminary and, although oncoprotein expression was detected, no positive case demonstrated deoxyribonucleic acid amplification.