Abstract
<jats:p>Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive non-Hodgkin lymphomas and is characterized by pronounced molecular heterogeneity that is not always fully captured by standard histopathological assessment. At present, analysis of circulating tumor DNA (ctDNA) is regarded as a promising liquid biopsy tool that enables non-invasive molecular tumor profiling, assessment of tumor burden, and dynamic monitoring of minimal residual disease (MRD). Modern analytical platforms, ranging from PCR-based technologies to next-generation sequencing, including CAPP-Seq and PhasED-Seq, have substantially expanded the possibilities of molecular monitoring in DLBCL. This review summarizes data on the biological characteristics of ctDNA and contemporary methods for its analysis, as well as evidence regarding the concordance between ctDNA mutational profiles and tumor tissue. Particular attention is paid to the clinical significance of baseline ctDNA levels, early assessment of molecular eradication of the tumor clone, MRD status after completion of therapy, and molecular monitoring during remission. The principal limitations of clinical integration are also discussed, including insufficient standardization of the analytical workflow, the influence of clonal hematopoiesis, and the absence of completed interventional studies demon-strating improved clinical outcomes when therapy is modified according to molecular status. Thus, ctDNA currently represents a highly informative prognostic biomarker in DLBCL; however, its full implementation in routine clinical practice requires further standardization, validation, and confirmation of its role in treatment selection within personalized strategies.</jats:p>