A report in this issue of Cancer on disparate follow-up of abnormal prostate-specific antigen (PSA) levels among younger black men in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial raises new concerns regarding the adequacy of evidence available to assess the balance of risk and harms of PSA-based screening for these men. Clinicians should analyze published screening recommendations with an understanding of the data gaps regarding this population, and shortcomings in the existing evidence base must be addressed.