Advanced sequencing technologies, such as cancer personalized profiling by deep sequencing (CAPP-seq), have demonstrated that ctDNA can detect hallmark genetic alterations associated with DLBCL subtypes, including mutations of MYD88, CD79B, and EZH2, making it a useful tool for disease genotyping, enabling molecular classification of DLBCL and guiding targeted therapies. This evidence concerns the gene EZH2 and diffuse large B-cell lymphoma.