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Cell-free DNA (cfDNA) is comprised of free-floating DNA fragments released into blood, cerebral spinal fluid, urine, and other bodily fluids secondary to apoptosis, necrosis, NETosis, physical cell damage, and/or active secretion due to an underlying (patho)physiologic process including pregnancy, autoimmune disease, infection, trauma, organ transplant, or neoplasia. The potential of cfDNA is therefore substantial, with implications in prenatal screening and management of cancer patients. But distinguishing hype from clinically validated indications is a daunting task, one made more difficult by rapidly advancing technologies and evolving practice recommendations. After viewing this lecture, participants should be able to: 1. Discuss the basic concepts, benefits, and limitations of cfDNA testing. 2. Recognize settings where cfDNA testing has become standard of care. 3. Identify clinical settings where cfDNA tests lack evidence of clinical utility. Vera Paulson, MD, PhD Assistant Professor, Genetics Division Associate Director, Genetics and Solid Tumors Laboratory Department of Laboratory Medicine & Pathology University of Washington 01/04/23