The diagnosis of prostate cancer on needle biopsy is based on a constellation of histologic features. There are, however, three histologic findings that are diagnostic of prostate carcinoma: perineural invasion (PNI), mucinous fibroplasia, and glomerulations. We prospectively identified core needle biopsies during a 5-month period in which one of these three entities was the key diagnostic feature of carcinoma within the biopsy specimen. Of 1480 consult cases reviewed, the following were key features to the diagnosis of very limited carcinoma: PNI (n = 9; 0.6%), mucinous fibroplasia (n = 2; 0.1%), and glomerulations (n = 0). To assess the incidence of PNI as the key feature, we also analyzed reports from Dianon during a 1-year period. Of approximately 16,300 Dianon needle biopsies with cancer, 12(0.07%) cases had PNI as the key diagnostic feature. Six of these 12 cases were also consult cases. Of the total of 15 cases with PNI, cancer was limited with 11 of the cases showing involvement of only one nerve. The median number of glands per nerve was five (range, 1-15). In addition to PNI, malignant cytologic features included amphophilic cytoplasm in 11 of 11 assessable cases and nuclear enlargement and hyperchromasia in 11 of 15 cases. Other malignant features were limited. Twelve cases showed rare to no visible nucleoli. Two cases had eosinophilic intraluminal debris. Blue mucin, crystalloids, and mitoses were absent in all cases. Nine of the 15 cases of PNI and the two cases of mucinous fibroplasia were verified as carcinoma with immunohistochemistry using high molecular weight cytokeratin. In rare cases, PNI is virtually the sole finding necessary to establish the diagnosis of carcinoma on needle biopsy. Although mucinous fibroplasia and glomerulations are also considered diagnostic of carcinoma, their occurrence alone without more conventional forms of carcinoma is even more rare.