While existing follow-on tests contingent on elevated PSA, so-called PSA reflex tests [16,17], and multiparametric MRI [18] reduce at least a fraction of unnecessary biopsies in men with PSA levels of 4–10 ng/mL, there is still a significant unmet clinical need for improved reflex tests capable of more accurately discriminating prostate cancer’s presence from other causes of elevated PSA while minimizing false negatives. This evidence concerns the gene KLK3 and Familial prostate cancer.