Abstract Introduction: The Signal Transducer and Activator of Transcription 3 (STAT3) pathway is thought to be phosphorylated (pSTAT3) and constitutively activated in prostate cancer (PCa). Previous results from our laboratory showed high pSTAT3 levels in PCa metastases. In the present study we investigated the expression of pSTAT3 in tissue microarrays of two cohorts of localized hormone-naïve PCa patients and correlated it with disease outcome. Methods: The expression of pSTAT3 in the nuclei of epithelial cells of prostatic glands was examined in two TMAs of paraffin-embedded prostatic tissue. The TMAs consisted of tissue originated from hormone-naïve radical prostatectomy patients from two different sites: Malmö (n=300) and Dublin (n=99). Results: In the Malmö cohort, the average expression levels of pSTAT3 in the epithelial cells of benign glands were significantly higher than in the cancerous glands. Patients with low pSTAT3 levels in the epithelial cells of the cancerous glands showed reduced times to biochemical recurrence, compared to those with higher levels; however, adding the pSTAT3 expression data to Gleason score or pathologic T stage did not improve their prognostic values. The results for the Dublin cohort showed similar trends. Conclusions: Low pSTAT3 expression in epithelial cells of cancerous prostatic glands in hormone-naïve PCa was associated with faster disease progression; however, pSTAT3 is unlikely to be a good biomarker in the early stages of PCa. Citation Format: Agnieszka Krzyzanowska, Nicholas Don-Doncow, Felicia-Elena Marginean, William Watson, Rebecka Hellsten, Anders Bjartell. Expression of activated STAT3 in the epithelial cells of hormone-naïve prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B078.