Despite the recent progress in targeted cancer therapies, the frequent development of drug resistance has proved to be a major hindrance. Rare mutations acquired by a small population of cells could benefit tumorigenesis and be cancer’s ticket to back door entry. However, identifying them is a challenge owing to the high error rates of current sequencing tools. A powerful sequencing method dubbed ‘Duplex Sequencing’ could significantly minimize this problem. By sequencing both strands of individual DNA molecules, Duplex Sequencing can identify ultra-low frequency mutations with a 10,000-fold higher resolution. We interviewed Dr. Jesse Salk, CEO of TwinStrand, to learn more about the technique and its potential in advancing cancer research.