We present 9 consult cases, the largest series to date, of colorectal adenocarcinoma involving the prostate. Mean age of patients at diagnosis was 61 years (range, 42-78 years). Six cases were initially diagnosed on needle biopsy and the others by transurethral resection. Three cases were diagnosed before biopsy of the colon, which led to the discovery of a primary colonic tumor. The mean interval between the detection of the primary colonic tumor and prostatic involvement in the other 6 cases was 30 months (range, 1-52 months). At diagnosis, the stages of colorectal carcinomas were pT1 (n=2), pT2 (n=2), pT3 (n=2), and pT4 (n=3). Two cases involved the prostate after the recurrence of rectal adenocarcinoma at the anastomotic site of the previous colonic resection. In most cases, the tumors were typical moderately differentiated with occasional poorly differentiated foci. Other histologic features included desmoplastic stromal reaction (100%, n=9), necrosis (77.8%, n=7), chronic inflammatory response (77.8%, n=7), cribriform pattern (66.7%, n=6), villous architecture (22.2%, n=2), mucin production (22.2%, n=2), signet-ring cells (11.1%, n=1), and perineural invasion (11.1%, n=1). Immunohistochemical stains were positive for beta-catenin in 6 of 6 cases, CDX2 in 6 of 6 cases, carcinoembryonic antigen in 7 of 7 cases, CK20 in 5 of 6 cases, high-molecular-weight cytokeratin in 5 of 6 cases, and alpha-methylacyl-CoA racemase in 3 of 6 cases. Stains were negative in all cases for prostate-specific antigen, P501S (prostein), and CK7. Six patients (66.7%) died of disease within an average of 34 months (range, 8-88 months) after diagnosis of prostatic involvement. There are critical therapeutic and prognostic implications for distinguishing between prostatic adenocarcinoma and colorectal carcinoma involving the prostate. Colorectal adenocarcinoma should be considered on prostate sampling when carcinoma exhibits either "dirty" necrosis, tall columnar epithelium with mucin production, mucin-positive signet-ring cells, villous architecture, or associated inflammation. Immunohistochemical stains for beta-catenin, CDX2, carcinoembryonic antigen, high-molecular-weight cytokeratin, prostate-specific antigen, P501S (prostein), CK20, and CK7 can be helpful in making a definitive diagnosis.