This Practice Point commentary discusses the findings and limitations of the study by Eastham and co-workers, which concludes that the location of a positive surgical margin after radical prostatectomy is important for prognosis. The study found that posterolateral margins markedly increased the risk of biochemical failure while apical margins did not. Posterolateral margin status was found to be even more important for predicting biochemical failure than was lymph node positivity or seminal vesicle invasion. For several reasons, however, these results might not be generalizable to other groups of patients or to clinically relevant end points, such as cancer-specific survival. Consequently, these data should be regarded as preliminary and should not inform therapeutic decisions. Instead, knowledge of the most-common sites of margin positivity might direct surgeons to examine any shortcomings in their surgical technique. We contend that positive margins can be prevented at even the most difficult-to-access locations if appropriate steps are taken.