Prostatic specific antigen (PSA) immunoreactivity is the most commonly used histological marker to identify epithelial cells of prostate origin. Unlike tissues from white men in which grade-related variability has been reported, the pattern of PSA immunoreactivity in prostatic tissues from black African men is presently unknown. This study was done to evaluate the pattern of PSA staining in sections of normal, benign hyperplastic and malignant prostatic glands from men from this sub-population. PSA immunostaining was done on 4-microm serial sections from archival specimens of benign prostatic hyperplasia (BPH) and carcinoma of the prostate (CaP) obtained from black African men using standard immunoperoxidase techniques. The intensity of PSA immunoreactivity of the glands was scored using a semi-quantitative method. PSA expression decreased with increasing de-differentiation of the tissue histotype with poorly differentiated tumours staining least. PSA immunoreactivity was strong in 100% of normal glands and 84% of BPH glands and moderate in the rest. In contrast, PSA immunopositivity was strong in 32% of CaP glands, moderate in 26%, weak in 34% and absent in 8%. Statistical comparison revealed that PSA expression was significantly higher in benign tissues (normal/ atrophic and BPH) than in CaP glands [p = < 0.0001]. Our findings show that PSA immunoreactivity is grade-related in prostatic tissues from black men and this has implications for clinical diagnosis and research. It also confirms the limitations of PSA-testing in diagnosing CaP, and indicates that newer immunohistochemical tests for malignant prostatic cells should be acquired by Sub-Saharan laboratories.