An anti-ERBB2 antibody, trastuzumab, has been shown to be highly efficient in the treatment of metastatic breast cancers overexpressing the ERBB2 gene. It has been suggested that overexpression and even amplification of ERBB2 may play a role in the development of prostate cancer. Here, we have analyzed gene copy number and expression of the ERBB2 gene in both androgen-dependent primary and metastatic tumors, as well as recurrent hormone-refractory tumors. The expression levels were compared to the expression of ERBB2 in breast cancers with or without ERBB2 gene amplification. Of 126 prostate tumors, chromogenic in situ hybridization (CISH) revealed only 1 case containing borderline (six to eight copies) amplifications of ERBB2. This hormone-refractory tumor, however, did not express ERBB2 protein. Immunohistochemical staining of ERBB2 protein was negative (0 or 1+ intensity) in all prostate samples (n = 124) analyzed. To quantitate the level of ERBB2 mRNA expression in prostate tumors (n = 34) and cell lines (n = 3), as well as in breast tumors (n = 30) and cell lines (n = 16), real-time reverse transcriptase-polymerase chain reaction (LightCycler) methodology was used. The expression level was similar in all prostate tumor types and corresponded to the level of expression in breast carcinomas without ERBB2 amplification. Breast tumors with ERBB2 amplification expressed, on average, approximately 20 times (P < 0.001) higher mRNA levels than prostate tumors or breast carcinomas without the gene amplification. In conclusion, the expression of ERBB2 in prostate cancer is relatively low, and is not altered during disease progression. Thus, it is unlikely that treatment modalities relying on the overexpression of ERBB2 gene will be useful in treating prostate cancer.