Primary signet-ring-cell carcinoma of the prostate is extremely rare. We report eight patients with prostatic adenocarcinomas containing significant numbers of signetring cells, one of whom presented initially with supraclavicular lymph node metastasis. Patient ages ranged from 50 to 80 years (mean, 67.5). None of the patients had received any form of therapy before biopsy or surgery. All patients presented with advanced disease (five with stage C and three with stage D). All tumors were poorly differentiated adenocarcinomas, M.D. Anderson Hospital system grade IV, Gleason's combined score of 9 or 10. The signet-ring cells were negative for neutral and acid mucins but immunoreactive for prostatic-specific antigen and prostatic acid phosphatase. Ultrastructurally, the signet-ring-cell appearance resulted either from the presence of intracytoplasmic lumina or from vacuoles. Signet-ring cells were also present at the metastatic sites. We conclude that (a) signet-ring-cell carcinoma of the prostate is a variant of poorly differentiated adenocarcinoma of the prostate; and (b) when a metastatic signet-ring-cell carcinoma with negative intracytoplasmic mucin is identified, a prostatic origin should be considered, and prostatic-specific antigen and prostatic acid phosphatase immunostaining should be performed.