Several biomarkers have been studied to avoid unnecessary biopsies resulting from suboptimal performance of prostate-specific antigen (PSA) testing. We aimed to assess the use of serum angiogenin as a prostate cancer diagnostic tool among candidates for biopsy. We selected 252 patients referred for ultrasound-guided transrectal prostate biopsy on the basis of an abnormal digital rectal examination and/or elevated total PSA. Serum angiogenin was quantitatively analyzed by solid-phase enzyme-linked immunosorbent assay. Results of the prostatic pathology assessment (cancer vs. noncancer) were defined by biopsy. The median serum angiogenin levels were significantly higher in patients with prostate cancer (median: 487 500 vs. 414 800 pg/ml, P=0.008). Among patients with baseline tPSA of 4.0 ng/ml or less, 37.5% had serum angiogenin less than 389 000 pg/ml (sensitivity: 88.9%; specificity: 45.2%), and the probability of having prostate cancer varied from 22.5% before testing to 6.7% among those with low angiogenin levels. When further restricting the analyses to a group of patients with even lower probability of having cancer, on the basis of tPSA and f/t PSA values, the evaluation of serum angiogenin did not contribute toward a meaningful variation in the post-test probability of cancer. In conclusion, serum angiogenin levels may be useful to distinguish between cancer and noncancer patients among the candidates for prostatic biopsy in regular clinical practice. Further investigation is needed among patients with low PSA levels and to understand the relation between this biomarker and the long-term survival of prostate cancer patients.