In this cohort study in which 408 men underwent 3 screening tests, an MRI score of 4 or 5 was associated with improved detection of clinically significant prostate cancer without an increase in the number of men who underwent biopsy or were overdiagnosed with clinically insignificant prostate cancer if prostate-specific antigen testing alone was used. The gene discussed is KLK3; the disease is Familial prostate cancer.