Prostate cancer is the most commonly diagnosed cancer in men and the second leading cause of cancer deaths. The serum prostate specific antigen (PSA) is the only bio-marker routinely used in screening. The aim of this study was to develop a system to test the presence of circulating prostate cells in men without a diagnosis of prostate cancer in relation with age, serum PSA levels and prostate biopsy by determining the co-expression of several markers such as CD82, HER-2 and matrix metalloproteinase 2 (MMP-2). For this purpose mononuclear cells were separated from blood using differential centrifugation and then prostate cells were identified by using standard immunocytochemical method. Results indicated that among 409 men screened for prostate cancer 16.6% were positive for circulating prostate cells. Cells were positive for MMP-2 and HER-2 in 100 and 14.3% of cases, respectively, without an association with age or PSA levels. However, CD82 protein expression was associated with older age and low grade tumors. It can be concluded that the study of circulating prostate cells with various markers could be a useful complementary screening test for prostate cancer in men with increased PSA level.