OBJECTIVE To determine whether p53 is an independent biomarker of prostate cancer outcome against currently used biomarkers in a cohort of conservatively treated prostate cancers with long-term follow-up available. PATIENTS AND METHODS We examined p53 expression by immunohistochemistry in a cohort of 705 patients with clinically localized prostate cancer, who were treated conservatively. Patients were selected through UK Cancer Registries. End-points included prostate cancer death and overall death rates. Standard biological variables, including diagnostic serum PSA, contemporary Gleason scoring, clinical staging and cancer extent were available. p53 expression was measured semi-quantitatively on microscopic examination and compared with current clinical biomarkers. RESULTS p53 over expression was a significant predictor of cause-specific survival (hazard ratio [HR] 2.95, 95% CI 2.05-4.25, P < 0.001) and overall survival (HR 2.37, 95% CI 1.84-3.05, P < 0.001). In multivariate analysis including competing biological variables p53 expression was still significantly linked to prostate cancer survival (HR 1.51, 95% CI 1.04-2.19, P = 0.03) and overall survival (HR 1.57, 95% CI 1.21-2.05, P = 0.001). CONCLUSIONS We conclude that p53 may have a role in the future assessment of newly diagnosed prostate cancer, as it significantly adds to the current prognostic model.