['Ductal carcinoma (DC) of the prostate is an entity distinct from the common acinar cancer (AC), both on clinical and morphological aspects. We aimed to analyze the expression of molecules involved in either hormonal signalling or androgen independent pathways, in DC compared to high grade AC.', 'A tissue microarray was constructed with samples from 24 cases of DC and 27 cases of high grade AC. Immunohistochemistry was performed using antibodies directed against: Ki67; androgen receptor (AR); PSA; 5alpha-reductase 1, 2, 3; oestrogen receptors alpha and beta (ERA and ERB); aromatase; Alpha keto reductase 1C3; Squalene epoxidase (SQLE); BCAR1; Src. Cell proliferation and ERB staining were significantly increased in DC compared to AC. In contrast, the expressions of enzymes SQLE, aromatase, and 5 alpha reductase 2, were higher in AC. Staining for BCAR1 and Src, markers associated with androgen-independent pathways, was increased in DC compared to AC. These differences remained significant after adjusting for pTNM stage.'] Does ductal carcinoma of the prostate show a different immunophenotype from high grade acinar cancer?