Abstract: The invention described herein relates in part to compositions, biomarkers and methods for diagnosis and prognosis of prostate lesions, including prostate cancer, including a tissue-based assay providing diagnostic and prognostic information related to prostate cancer. In some embodiments, the invention further relates to improvements in the ability to accurately diagnose prostate cancer, detect early-stage prostate cancer, and localize prostate lesions within the three-dimensional space of the prostate.