The immunoglobulin lambda locus (IGL) is located on chromosome 22 and encodes lambda light chains that form part of antibody molecules through V(D)J recombination. 1 IGL undergoes clonal rearrangement during B-cell development, which can be detected via multiplex PCR assays standardized by the BIOMED-2 collaborative study for diagnostic purposes. 1 However, IGL rearrangements have limited diagnostic value compared to immunoglobulin heavy chain (IGH) and kappa (IGK) loci; combined IGH and IGK analysis detects virtually all clonal B-cell proliferations, while IGL contribution is restricted. 1 In minimal residual disease (MRD) monitoring of pediatric B-acute lymphoblastic leukemia, IGK/IGL rearrangements identify only 5.5% of patients lacking trackable IGH clones, and IGL-based MRD is not independently prognostic at standard timepoints. 2 Clinically, IGL participates in chr22 translocations associated with lymphoproliferative disorders; the rare t(18;22)(q21;q11) translocation creates an IGL::BCL2 fusion predominantly observed in chr22 lymphocytic leukemia cases, potentially associated with shorter time to first treatment. 3 IGL gene rearrangement analysis using BIOMED-2 protocols improves clonality detection in Hodgkin lymphoma, achieving 94% sensitivity. 4