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Graduate School of Health Sciences, Kumamoto University; Department of Morphological and Physiological Sciences, Kumamoto University; Faculty of Life Sciences, Department of Neurology, Kumamoto University; Diagnostic Unit for Amyloidosis, Kumamoto University Hospital; Faculty of Life Sciences, Department of Hematology, Kumamoto University; Department of Surgical Pathology, Kumamoto General Hospital; Division of Informative Clinical Sciences, Kumamoto University Introduction: AL amyloidosis is a disease featuring deposition of Ig light chain (LC). Diagnosis is determined if the presence of LC in amyloid deposits is detected with anti-LC chain antibodies. Poor prognosis cases, like detected amyloid deposits in heart, require the prompt diagnoses. However, in several cases, the existence of LC is not detected within amyloid deposits with immunohistochemistry (IHC) using conventional anti-LC antibodies although monoclonal lambda light chain in serum or urine was proved. In such cases, we found deposition of particular light chain constant region (immunoglobulin light chain constant region 2: IGLC2) at amyloid tissues. Materials and Methods: Amyloid tissues were either stained with conventional anti-human lambda LC rabbit antiserum (DAKO PO-0130) or rabbit anti-IGLC2 antibodies (made by SIGMA ALDLICH). Deposited peptide within amyloid lesion was examined using Congo Red staining followed by combination of laser micro-dissection and mass-spectrometry combining (LC-MS/MS). Plasma cells were purified with CD138-immunomagnetic beads from bone marrow aspirated obtained from two cases. Recombination of LC DNA in purified plasma cells was analyzed using PCR and direct nucleic acid sequencing. Results and Discussion: LC-MS/MS analysis revealed the presence of IGLC2 in all cases without showing positive signal by conventional antibody. Recombination of IGLC2 was detected in plasma cells. Deposition of IGLC2 was confirmed by IHC using anti-IGLC2 antibodies. The present data imply that “IGLC2-related amyloidosis” might be overlooked by conventional IHC unless utilizing mass-spectrometry. Utilization of antibodies for IGLC2 should contribute to improve quality of diagnosis for AL-amyloidosis. We consider that investigation of IGLC2 is important for not only making diagnosis but also analyzing pathogenesis of AL-amyloidosis.