There is limited published data regarding the significance of the number or position of nucleoli and the presence of apoptotic bodies in diagnostically challenging cases of adenocarcinoma of the prostate on needle biopsy material. One hundred consecutive prostate cancers on needle biopsy were sent because of diagnostic difficulty to an expert in urological pathology, and the remaining normal benign prostatic glands on the same core were evaluated for the number and location of nucleoli and for the presence of mitotic figures and apoptotic bodies. The Gleason scores of the cases were 6 (86%), 7 (9%), and 8 to 10 (5%). For comparison, the same parameters were evaluated in mimickers of cancer on needle biopsy from other cases, including partial atrophy (n = 135), fully developed atrophy (n = 89), adenosis (n = 50), prostate glands with acute inflammation (n = 50), and high-grade prostatic intraepithelial neoplasia (n = 100). Findings were recorded under high dry magnification (x40) using hematoxylin and eosin-stained sections. Although the number and position of nucleoli did not discriminate between cancer and benign mimickers, mitotic figures and apoptotic bodies were more commonly seen in cancer. Apoptotic bodies in particular were seen fairly frequently (34%) in prostatic adenocarcinoma (also seen in 13% of high-grade prostatic intraepithelial neoplasia), yet rarely in benign mimickers on needle biopsy. Our findings indicate that the presence of apoptotic bodies should be added to the list of histological features that are helpful in the diagnosis of challenging cases of prostate cancer on needle biopsy.