OBJECTIVE To evaluate the involvement of thioredoxin reductase (TxnR), thioredoxin (Trx) and peroxiredoxins (Prdx) in prostate cancer (PCa) and to assess the potential prognostic importance of these redox-regulated pathways. METHODS Expression of the isoforms TxnR2, Trx1 and Prdx2 was studied by immunohistochemistry on tissue microarrays (TMAs). In a prognostic TMA, 294 primary cases of PCa with a median follow-up of 49 months were stained for Trx1 and Prdx2. Another TMA containing benign prostatic tissue, atrophy, high grade prostatic intraepithelial neoplasia (HGPIN) and PCa from 40 patients was stained with all 3 antibodies. RES ULTS: All 3 proteins showed similar expression patterns, with the highest immunoreactivity in HGPIN followed by atrophy, PCa and benign tissue. TxnR2, Trx1 and Prdx2 were overexpressed in HGPIN and PCa compared with benign tissue (p < 0.001), and Trx1 and Prdx2 were also overexpressed in HGPIN compared with PCa (p < 0.001). Trx1 and Prdx2 did not correlate with biochemical recurrence. CONCLUSIONS This study demonstrates up-regulation of the redox pathway proteins in PCa and its precursor lesions. The pathogenetic role of the redox system remains to be investigated.