Early diagnosis of systemic light-chain amyloidosis (AL) is needed because 25% of patients die within months of diagnosis. In patients with monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM) of the λ isotype, we explored the use of 2 screening variables: a free light chain difference of 23mg/L between λ and k and presence of IGLV genes that occur more frequently in AL. Patients contacted us and we sent HIPAA release and consent forms for discussion by phone. Their physicians were not involved. We enrolled patients with λ MGUS or SMM who met the FLC criteria with no prior biopsies showing amyloid. They sent us blood or marrow specimens for IGLV gene amplification by RT-PCR; we also assessed the feasibility of next generation sequencing (NGS) for IGLV genes. We informed patients and their physicians of results suggesting further evaluation for AL. We enrolled 21 patients, 19 SMM and 2 MGUS, receiving blood (n=21) or marrow (n=5) specimens. We identified IGLV genes in 86% (18/21) of cases. Four of the 18 IGLV genes were not AL-related and 3 of these 4 progressed to myeloma requiring therapy; the 4th was screened for amyloid and was negative. Fourteen patients with AL-related genes had comprehensive evaluations and two with SMM had AL. RT-PCR and NGS identified the AL-related LV2-14 in those two and also the monoclonal IGLV genes from all of the marrow but not the peripheral blood samples. We concluded that these variables may be useful in screening for AL in λ MGUS and SMM patients and acquired support for a small multi-center study employing marrow samples only.