Granular cytoplasmic pigment is frequently observed in prostatic epithelium, and may cause confusion with ejaculatory ductal and seminal vesicular epithelium. We evaluated the distribution and histochemical and immunohistochemical phenotype of pigment in nine serially sectioned, whole-mounted prostatectomy specimens with carcinoma. Golden yellow-brown pigment was found in prostatic glandular epithelium in eight cases (89%) of nine, varying from inconspicuous and focal to extensive and diffuse. It was usually located in the basal portion of the secretory (lumenal) cell layer, but was also observed throughout the cytoplasm, and rarely seen in basal cells. Stromal pigment was observed in seven cases (78%) of nine and was patchy and inconspicuous. Epithelial pigment was observed throughout the prostate (transition zone, 67%; central zone, 56%; peripheral zone, 89%; and periurethral glands, 56%). Focal pigment was observed in high-grade prostatic intraepithelial neoplasia in seven cases (78%) of nine and one case (11%) of nine cases of adenocarcinoma. The epithelial pigment was histochemically similar to lipofuscin pigment (Fontana-Masson positive, bleached by permanganate reaction, Prussian blue negative, and Ziehl-Neelsen positive); S100 protein immunohistochemical stains were negative. Our results indicate that pigment is frequently present in the prostatic epithelium of all zones, at least focally, and has histochemical similarities to pigment in the seminal vesicular epithelium. Awareness of prostatic epithelial pigment is important, and the differential diagnosis of pigmented epithelium in scant specimens such as those obtained from needle biopsies includes normal and neoplastic prostatic epithelium, seminal vesicle epithelium, and ejaculatory duct epithelium.