OBJECTIVE To assess the additional prognostic value of the molecular markers EZH2, MIB-1, p27kip1 and BMI-1 on needle biopsies from men with low-risk prostate cancer, as this disease in needle biopsies shows a heterogeneous clinical outcome, and while it is known that the expression of these tissue markers is predictive of the clinical outcome after radical prostatectomy (RP) their value in prostate biopsies is largely unknown. PATIENTS AND METHODS The study included men participating in a screening study, diagnosed with low-risk prostate cancer and subsequently treated with RP. Immunohistochemical staining for EZH2, MIB-1, p27kip1 and BMI-1 on the needle biopsies were (semi)quantitatively scored and expression levels were related to significant disease at RP. Clinical low-risk prostate cancer was defined as a prostate-specific antigen (PSA) level of < 10 ng/mL, clinical T-stage < 2, biopsy Gleason score < 6, a PSA density of < 0.20 ng/mL/g and two or fewer positive cores. Significant PC at RP was defined as presence of any of extracapsular extension, Gleason pattern 4/5, or tumour volume >= 0.5 mL. RESULTS In all, 86 biopsy specimens were included; there was high EZH2 expression (> 1.0%) in 42% and a low p27kip expression (< 90%) in 63%. Significant disease was present in 44 (51%) RP specimens. A high EZH2 (odds ratio 3.19, P = 0.043) and a low p27kip1 (4.69, P = 0.036) were independent predictors for significant prostate cancer at RP. CONCLUSIONS The determination of EZH2 and p27kip1 on diagnostic needle biopsies supports the selection of men with indolent prostate cancer at RP. Especially p27kip1 could improve the pretreatment risk assessment of patients with low-risk prostate cancer.