Classically, adenosis has been described as occurring in the transition zone of the prostate, a region not routinely sampled with needle biopsies. However, with urologists performing more needle biopsies, we have seen an increasing number of cases of adenosis in needle biopsies of the prostate. To better characterize the histologic features of adenosis present in needle biopsy specimens, we reviewed 63 needle biopsies of the prostate containing a total of 75 foci of adenosis. Of the 63 cases, 51 (81%) were seen in consultation by one of the authors, and in approximately 80% of these cases, the differential diagnosis included low-grade adenocarcinoma. Crystalloids were present in 18 foci (24%), a minimally infiltrative growth pattern in 10 foci (13%), prominent nucleoli in 10 foci (13%), scattered single cells in eight foci (11%), mitoses in two foci (3%), and blue-tinged muci-nous secretions in two foci (3%). Immunohistochemistry was performed on 29 (39%) foci to rule out adenocarcinoma. Intraluminal crystalloids, a minimally invasive growth pattern, and single cells occur with sufficient frequency in adenosis, such that their presence is not useful in distinguishing low-grade adenocarcinoma from adenosis; 62 (83%) of the foci of adenosis were found to contain none of the remaining histologic features (mitoses, blue-tinged luminal secretions, prominent nucleoli), whereas 12 foci (16%) had one of the features and one focus (1%) had two features. Adenosis should always be in the differential diagnosis when one is considering low-grade carcinoma on needle biopsy. The key feature of adenosis is the merging of small crowded glands with surrounding benign glands; in contrast, the small glands of adenocarcinoma differ in their cytoplasm, nuclei, or luminal contents from adjacent benign glands.