Oncoprotein 18 (Op18) is an intracellular phosphoprotein that has been shown to be overexpression in a number of human malignancies. In the present report we have studied the pattern of Op18 expression on normal, hyperplastic, and malignant prostatic tissue as well as in rat prostatic tumor lines. One of the objectives of the present work was to establish whether the level of Op18 expression can be used as a prognostic marker in human prostatic adenocarcinoma. To that end, sections from normal, hyperplastic, and malignant human prostatic tissue were examined by immunohistochemistry for expression of Op18. In the normal and hyperplastic prostate, Op18 expression was observed in basal glandular epithelial cells, whereas the columnar luminal epithelial cells were not stained by the anti Op18 antibodies. In highly differentiated prostatic cancers occasional epithelial cells were stained, while in poorly differentiated tumors most of the epithelial cells contained Op18 immunoreactivity. The staining pattern was similar in the primary prostatic tumor and in the regional lymph node metastases. Most importantly, a limited survey of prostatic cancer patient samples (n = 40) showed a significant correlation between the fraction of Op18 immunoreactive cells and survival. Studies of a rat prostatic tumor model, showed that only a few cells were stained in the highly differentiated Dunning R3327PAP tumor, while most cells were stained in the anaplastic AT1 rat prostatic tumor. Interestingly, castration of rats resulted in an increased Op18 immunoreactivity, within 14 days, in the highly differentiated rat R3327PAP prostatic tumor. In conclusion, the level of Op18 expression seems to be related to cellular differentiation, histological grade, and survival in prostatic cancers. These findings show that Op18 immunoreactivity may be useful as a prognostic marker in prostatic cancer. In addition it may help in the differentiation between highly differentiated prostatic tumors and non-malignant conditions.