On SurgOnc Today®, Patrick S. Sullivan, MD, Maria Diab, MD, and Nader Hanna, MD, discuss the use of liquid biopsy or ctDNA to identify molecular disease prior to clinically detectable disease. Molecular detection of ctDNA can be used to detect minimal residual disease (MRD) which is residual cancer cells detected only by molecular techniques but not by conventional testing. Molecular testing of ctDNA can also be used to detect molecular relapse. This allows the molecular detection of occult disease during adjuvant therapy or during surveillance. This information can be prognostic and help determine patients with increased risk of recurrent disease who may benefit from adjuvant therapy and targeted chemotherapy. It can also be used for prediction for adjuvant chemotherapy. In addition it can be used for de-escalation of chemotherapy by identifying patients who would not gain the benefit of chemotherapy. There are 2 approaches for detecting MRD. One is tumor agnostic and the second is tumor informed. The tumor informed has higher sensitivity by identifying mutations in the tumor tissue and tracking these mutations in the plasma.