Introduction: The cell surface endopeptidase CD10 (neutral endopeptidase) and nuclear factor-kappa B (NF-kappa B) have been independently associated with prostate cancer (PC) progression. We investigated the correlations between these two factors and their prognostic relevance in terms of biochemical (prostate-specific antigen, PSA) relapse after radical prostatectomy (RP) for localized PC. Patients and Methods: The immunohistochemical expression of CD10 and NF-kappa B in samples from 70 patients who underwent RP for localized PC was correlated with the preoperative PSA level, Gleason score, pathological stage and time to PSA failure. Results: CD10 expression was inversely associated with NF-kappa B expression (p < 0.001), stage (p = 0.03) and grade (p = 0.003), whereas NF-kappa B was directly related with stage (p = 0.006) and grade (p = 0.002). The median time to PSA failure was 56 months. CD10 and NF-kappa B were directly (p < 0.001) and inversely (p < 0.001) correlated with biochemical recurrence-free survival, respectively. CD10 expression (p = 0.022) and stage (p = 0.018) were independently associated with time to biochemical recurrence. Conclusion: Low CD10 expression is an adverse prognostic factor for biochemical relapse after RP in localized PC, which is also associated with high NF-kappa B expression. Decreased CD10 expression which would lead to increased neuropeptide signaling and NF-kappa B activity may be present in a subset of early PCs. Copyright (C) 2012 S. Karger AG, Base