AbstractLymphomas are heterogeneous tumors with striking genetic diversity and variable outcomes even within pathologic diagnoses. Treatment response assessment relies on radiologic and nuclear scans, which cannot detect disease at the molecular level. Molecular tumor analyses require invasive tissue biopsies that cannot accurately capture spatial tumor heterogeneity within each patient. Circulating tumor DNA (ctDNA) is a minimally invasive and highly versatile biomarker that overcomes fundamental limitations of imaging scans and tissue biopsies and may aid clinical decision-making in lymphoma. In this review, we highlight the key established principles regarding ctDNA in lymphoma and emphasize the important research questions and future directions.Significance:ctDNA is an emerging biomarker for lymphomas that noninvasively provides genotypic information and can measure the effectiveness of treatment by detecting the presence of minimal residual disease. Key principles have emerged related to ctDNA for lymphoma, but further studies are needed to standardize its use and establish clinical utility.