HER-2/neu may play a role in prostate carcinogenesis. The aim of this study was to use the expression of HER-2/neu as a molecular marker for the detection of circulating tumour cells (CTCs) in the blood of patients with prostate cancer (PC). Blood samples were collected from 42 patients with PC and nine healthy volunteers. Immunomagnetic beads were used to harvest epithelial cells from peripheral blood mononuclear cells. Total RNA was extracted and reverse transcribed before analysis by real-time PCR with HER-2/neu-specific primers. CTCs were HER-2/neu positive in six out of 11 (54%) patients with metastatic disease and in three out of 31 (9.6%) patients with localised PC (P=0.004). In blood samples from nine healthy volunteers, we detected no expression of HER-2/neu. The present method appears to be minimally invasive, highly sensitive and a specific approach for detecting CTCs in PC. Furthermore, it may help better target HER-2/neu in advanced PC.