Recent studies have shown that patients with prostate carcinomas exhibiting ductal differentiation have an unfavourable prognosis compared with those with purely acinar adenocarcinomas. We studied the expression of nine immunohistochemical markers to evaluate their value in delineating carcinomas with and without ductal differentiation. Thirteen tumours showing cellular characteristics and growth patterns typical of ductal differentiation were identified among 110 analysed prostatectomy specimens. The levels of cytoplasmic expression of chromogranine A (69% vs 19%, p = 0.0003) and nuclear expression of p53 (76% vs 12%, p < 0.0001) as well as nuclear expression of Ki-67 (69% vs 26%, p = 0.0047) in the tumour cells, were found to be statistically significantly different in the two tumour categories. Assessment of chromogranine A, p53 and Ki-67 in prostate carcinoma may serve as useful adjunctive diagnostic tools for delineating more aggressive prostate cancer cases exhibiting ductal differentiation.