The prostate biopsy pathology report represents a critical document used for decision-making in patients diagnosed with prostate cancer, yet the content exceeds the health literacy of most patients. We sought to create and compare the effectiveness of a patient-centered prostate biopsy report compared with standard reports.Using a modified Delphi approach, prostate cancer experts identified critical components of a prostate biopsy report. Patient focus groups provided input for syntax and formatting of patient-centered pathology reports. Ninety-four patients with recent prostate biopsies were block randomized to the standard report with or without the patient-centered report. We evaluated patient activation, self-efficacy, provider communication skills, and prostate cancer knowledge.Experts selected primary and secondary Gleason score and the number of positive scores as the most important elements of the report. Patients prioritized a narrative design, non-threatening language and information on risk classification. Initial assessments were completed by 87% (40/46) in the standard report group and 81% (39/48) in the patient-centered report group. There were no differences in patient activation, self-efficacy, or provider communication skills between groups. Patients who received the patient-centered report had significantly improved ability to recall their Gleason score (100% vs. 85%, p = 0.026) and number of positive cores (90% vs. 65%, p = 0.014). In total, 86% of patients who received the patient-centered report felt that it helped them better understand their results and should always be provided.Patient-centered pathology reports are associated with significantly higher knowledge about a prostate cancer diagnosis. These important health information documents may improve patient-provider communication and help facilitate shared decision-making among patients diagnosed with prostate cancer.