Decreased expression of CD44 is an independent prognostic marker for surgically treated prostate cancer. To investigate immunohistochemically defined CD44 expression in primary and metastatic prostate cancer, 2 groups of patients undergoing radical prostatectomy for clinically localized prostate cancer were studied. (1) pN1 group: 23 patients, finally staged pN1, of whom the radical prostatectomy specimen and the lymph nodes were investigated to establish a correlation between CD44 expression in the concurrently resected primaries and metastases; (2) pN0 group: 23 patients with pN0 disease matched for pT stage and Gleason sum score with the pN1 patients. Progression rates based on serum prostate‐specific antigen (PSA) levels could be determined in 42 of these 46 patients. In addition, 28 distant metastases were studied. A CD44 score of < 10% was found in 22 of the 23 lymph node metastases (96%) and in 20 of the corresponding radical prostatectomies. In the pN0 group this was observed in only 6 out of 23 specimens. In most of the distant metastases CD44 scores were < 10%. Patients with pN0 disease and > 10% CD44‐positive tumor cells had a significantly better prognosis than the other patients who were not significantly different from each other. CD44 expression is thus strongly reduced in prostate cancer metastases as well as in the corresponding primary tumors. This reduction may be used to predict the N stage clinically, provided that CD44 scores can be determined reliably on preoperative biopsy specimens. Int. J. Cancer (Pred. Oncol.) 84:478–483, 1999. © 1999 Wiley‐Liss, Inc.