The use of biomarkers in screening and optimization of the diagnostic strategy may avoid unnecessary biopsies and improve the prostate biopsy performance. Screening for prostate cancer (Pca) may provide a small benefit in disease-specific mortality over 10 years but it does not improve overall mortality. These benefits should be weighed against the potential complications from biopsies and subsequent treatment, and the risk of overdiagnosis and overtreatment. PSA, if used alone, is insufficient. Integration of genomic tests may advance the diagnosis of Pca. Prostate health index, 4 kallicrein score combining PSA isoforms improve the AUC in the diagnosis setting. The genomic rearrangement occurs in about 30-50% of prostate cancer patients having a specifity of 93% and a PPV of 94%. Mi prostate score combines PCA3 with TMPRSS2 ERG to estimate risk of Pca and thus to help decision making for prostate biopsy. miRNAs seems useful tools for diagnosis and prediction of clinical outcome of Pca patients. PSA screening has to be associated with the mpMRI in order to avoid un-necessary biopsies. The circulating tumor cells identification using immuno cyto chemistry techniques seems the most promising screening test but it needs further evaluation. Integration with genomic tests (such as micro RNA) might turn out imperative in the prediction of clinical outcome.