Parathyroid hormone-related protein (PTHrP) is produced by a variety of malignant tumors and has been implicated as a major cause of humoral hypercalcemia of malignancy. Expression of PTHrP in prostate cancer tissue was studied immunohistochemically using 33 radical prostatectomy specimens from patients with clinically localized carcinoma of the prostate. None of these patients demonstrated hypercalcemia prior to the surgery. Acetone-methyl benzoate-xylene-processed, paraffin-embedded tissues were stained with a validated mouse monoclonal antibody to an amino acid fragment, PTHrP(109–141), using the streptavidin-peroxidase enzyme conjugate method. All cases (33 of 33; 100%) studied demonstrated some degree of immunoreactivity throughout the cytoplasm of the tumor cells, but immunostaining was absent from inflammatory and stromal cells. The intensity of the staining appeared to directly correlate with increasing tumor grade. The widespread immunohistochemical localization of PTHrP in carcinoma of the prostate suggests that PTHrP may play some local role in the growth of transformed cells in the prostate. Furthermore, overexpression of PTHrP may be a possible marker to evaluate the malignant potential of carcinoma of the prostate.