Intraductal carcinoma of the prostate (IDC-P) has been described in radical prostatectomies. However, there is limited information as to its histologic features and clinical significance when seen on prostate biopsy. A total of 27 cases of prostate biopsies with only IDC-P (ie no infiltrating cancer anywhere on the biopsy) were studied from the consult files of one of the authors. IDC-P was defined as malignant epithelial cells filling large acini and prostatic ducts, with preservation of basal cells forming either: (1) solid or dense cribriform patterns or; (2) loose cribriform or micropapillary patterns with either marked nuclear atypia (nuclear size 6 x normal or larger) or comedonecrosis. The numbers of cores involved by IDC-P in the biopsies ranged from 1 to 7, with >1 core involved in 17 cases. The architectural patterns of IDC-P were solid (12), dense cribriform (19), loose cribriform (17), and micropapillary (5). More than one pattern was present in 24 of 27 cases. The cytological features frequently observed in IDC-P were marked pleomorphism (18), non-focal comedonecrosis (22), and mitoses (20). Basal cells were observed on regular hematoxylin and eosin stained slides in 14 cases; in all the cases, basal cells were confirmed by immunohistochemical stains for high molecular weight cytokeratin (n=25) and/or p63 (n = 4). After the diagnosis of IDC-P on prostate biopsies, patients were treated by radical prostatectomy (6), radiation (7), hormone (5), combined radiation and hormone (1), or watchful waiting (2). The follow-up information was not available for six patients. The follow-up times ranged up to 4 years with an average of 2.1 years. In all six radical prostatectomy specimens, high-grade infiltrating carcinoma with Gleason score 8 or 9 was present with five cases also revealing prominent IDC-P. Non-focal extraprostatic extension of carcinoma was observed in five of the six prostatectomy cases with two cases also demonstrating vascular invasion. Three of 16 patients who did not receive radical prostatectomy developed bone metastases. Our study indicates that IDC-P on prostate biopsies is frequently associated with high-grade cancer and poor prognostic parameters at radical prostatectomy as well as potentially advanced disease following other therapies. These findings support prior studies that IDC-P represents an advanced stage of tumor progression with intraductal spread of tumor. Consideration should be given to treat patients with IDC-P on biopsy aggressively even in the absence of documented infiltrating cancer.