We demonstrated previously elevated caveolin-1 expression in metastatic mouse and human prostate cancer cells both in vitro and in vivo. In this study, we analyzed its prognostic value for progression of clinically confined human prostate cancer. Immunohistochemical staining with a caveolin-1-specific antibody was performed on routinely processed paraffin sections from 189 radical prostatectomy specimens. Caveolin-1 immunoreactivity was evaluated in association with patients' age, race, preoperative prostate-specific antigen, clinical stage, and pathological features including Gleason score, extraprostatic extension, status of surgical margins, and time to disease progression after surgery. Positive caveolin-1 immunostaining was detected in 47 of the 189 cancers (25%) and correlated positively with Gleason score, positive surgical margin, as well as lymph node involvement (P = 0.0071, 0.0267, and 0.0399, respectively). In lymph node-negative cancers (n = 162), caveolin-1 immunoreactivity predicts a shorter time to disease progression after surgery (P = 0.0033, univariate analysis). Multivariate analyses that included caveolin-1 and other prognostic pathological markers identified positive caveolin-1 immunostaining as an independent predictor for time to disease progression (P = 0.0186). Thus, our study establishes caveolin-1 as a novel prognostic marker for clinically confined human prostate cancer.