Duplex Sequencing™ technology is a new error-corrected NGS method that improves sequencing accuracy 100,000-fold. This increase in accuracy opens the door to significant reductions in time spent in drug development, allowing measurement of a compound’s carcinogenic risk months or even years earlier than current methods. DS technology now permits early measurement of ultra-rare new mutants. We will discuss the technology, clinical applications and then explore nonclinical safety assessment applications. Mouse and rat mutation data will be presented from various mutagens, tissues and genes. Mutant frequency data and mutational “fingerprint” data will be discussed in context of human tumors. Plans for collaborative qualification through the HESI Genetic Toxicology Technical Committee will be discussed.