A method of distinguishing prostate cancer from benign prostatic hyperplasia (BPH) is provided. The mathematical combination or ratio of proPSA and BPSA serum or tissue markers may be used for distinguishing benign prostatic hyperplasia (BPH) from prostate cancer. It is the discovery of the present invention that BPSA is preferentially elevated in transition zone prostate tissue whereas pPSA is elevated in the peripheral zone of prostate tissue. A kit for aiding in distinguishing BPH from prostate cancer is also provided.