Morphological analyses of prostate specimens after brachytherapy are rare and present a challenge to the pathologist due to an inherent difficulty in determining the difference between dying glands and surviving cancer cells. We have taken the opportunity to analyze an autopsy specimen in an attempt to set criteria by which one can analyze post-radiation therapy prostate biopsies. The patient had undergone brachytherapy and experienced a clinical complete response based on undetectable prostate-specific antigen and died of unrelated disease. Immunohistochemical studies were performed with the following antibodies: p63, P504S/AMACR and high molecular weight cytokeratin (HMWCK). Using a combination of molecular staining techniques, we were able to conclude that there were no viable tumor cells present in the specimen. The requirement to use various techniques to come to this conclusion demonstrates inherent difficulty in differentiating viable tumor cells from those that may appear viable but have been affected by ionizing radiation and will be unable to undergo cell division. It is crucial that this uncertainty is kept in mind in making further management decisions in patients who have undergone radiation therapy and follow-up biopsy of the prostate gland.