Abstract Objectives: The purpose of this study is to evaluate the role of soluble E-cadherin as a serum marker and bcl-2 and DNA content as tissue markers in characterization and management of prostatic adenocarcinoma (PC) among Egyptian males. Design and Methods: The study group included 71 patients with prostatic adenocarcinoma, 30 patients with benign prostatic hyperplasia (BPH), and 20 normal male subjects. Serum soluble E-cadherin (sE-cadherin) and PSA were quantified by ELISA and MEIA (microparticle enzyme immunoassay) techniques, respectively. Tissue samples were investigated for bcl-2 chromosomal translocation t(14;18) by polymerase chain reaction (PCR) together with detection of bcl-2 protein expression by immunohistochemistry. The results were correlated with DNA content (as defined by flow cytometric analysis) and also with traditional clinicopathologic parameters. Results: Our data revealed that, serum PSA was superior to sE-cadherin as a marker for PC with a sensitivity of 83% compared to 59% in case of E-cadherin at the same specificity (96.6%). Combination of both markers raised the sensitivity to 90%. E-cadherin correlated with Gleason score. Ploidy status, synthetic phase fraction (SPF), and proliferation index (PI) correlated significantly with tumor Gleason score. PI was also correlated to clinical stage. bcl-2 protein was overexpressed in 14% of PC and it showed a trend for correlation with tumor Gleason score (p = 0.06). We failed to detect chromosomal t(14;18) in the bcl-2 gene in all the studied tumors. Conclusions: E-Cadherin is a clinically useful biomarker in PC specially in combination with PSA. DNA content changes and bcl-2 oncogene may account for tumorogenesis and may assist in prognostication of PC.