Prostate-specific antigen (PSA) screening has increased prostate cancer awareness since its implementation as a screening tool almost 25 years ago, but, due to the largely indolent course of this disease and the unspecific nature of the PSA test, increased incidence has largely been associated with cancers that would not go on to cause death (clinically insignificant), leading to an overdiagnosis challenge and an ensuing overtreatment consequences. The gene discussed is KLK3; the disease is cancer.