Longitudinal study of clonal evolution. (A) FL has a spectrum of clinical behaviors that evolve over several years. The time from diagnosis to first treatment and to first relapse vary significantly across patients and are unpredictable at diagnosis. (B) Tools to study the biology of FL over time are evolving beyond tissue biopsies and include liquid biopsies at key landmark time points (time of diagnosis, time of first treatment, and time of first relapse). Liquid biopsies additionally empower longitudinal monitoring of the clinical response and clonal evolution. Excisional biopsies provide material for histological studies (tissue biopsy) and dissociated single cell and sequencing methods (cell suspension). (C) Future workflows may include profiling multiple LNs via multiomic technologies and integrating this data to obtain a holistic portrait of cell-intrinsic and extrinsic factors governing clinical outcome.