OBJECTIVES To investigate whether cysteine-rich secretory protein 3 (CRISP-3) and/or beta-microseminoprotein (beta-MSP) expression in diagnostic prostate needle biopsies have predictive value for prostate cancer (PC) on radical prostatecomy (RP). To evaluate their potential clinical implementation in a preoperative setting. PATIENTS AND METHODS In total, 174 participants from the European Randomized Study of Screening for Prostate Cancer, Rotterdam section, treated by RP for PC were included in the present study. CRISP-3 and beta-MSP immunohistochemistry was performed on corresponding diagnostic needle biopsies. Outcome was correlated with clinicopathological parameters (prostate-specific-antigen, PSA; number of positive biopsies; Gleason score, GS; pT-stage; surgical margins at RP) and significant PC at RP (pT3/4, or GS > 6, or tumour volume >= 0.5 mL) in the total cohort (n = 174) and in a subgroup with low-risk features at biopsy (PSA <= 10 ng/ml, cT <= 2, PSA density <0.20 ng/mL/g, GS < 7 and <= 2 positive biopsy cores; n = 87). RESULTS beta-MSP and CRISP-3 expression in PC tissue was heterogeneous, with variable staining intensities occurring in the same tissue specimen. High expression of beta-MSP significantly correlated with GS < 7 at RP; it was not a predictor for significant PC at RP neither in the total group (n = 174; odds ratio, OR, 0.319; 95% confidence interval, CI, 0.060-1.695; P = 0.180), nor in the low-risk group (n = 87; OR, 0.227; 95% CI, 0.040-1.274; P = 0.092). CRISP-3 expression was not related to clinicopathological parameters, and did not predict significant PC at RP in the total group (n = 174; OR, 1.056; 95% CI, 0.438-2.545; P = 0.904) or the low-risk group (n = 87; OR, 1.856; 95% CI, 0.626-5.506; P = 0.265). CONCLUSIONS High beta-MSP expression correlated with low GS in subsequent RP specimens, supporting the view that beta-MSP exerts a tumour-suppressive effect. No significant prognostic value of beta-MSP or CRISP-3 in prostate needle biopsies for significant PC at RP was found. beta-MSP or CRISP-3 do not have additional value in the therapeutic stratification of patients with PC.