The accurate detection of culprit lesion(s) in biochemical recurrence (BCR), or the setting of post-therapeutic relapse with elevated tumor marker levels (prostate-specific antigen, PSA), represents the most challenging step in prostate cancer management, which regularly escapes conventional imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), or bone scintigraphy. This evidence concerns the gene KLK3 and prostate cancer.