We present the immunohistochemical and biochemical identification of an amyloidoma localized to the cerebral white matter in a patient who shows no evidence of systemic or extracranial localized amyloid deposits. Immunohistologic and immunochemical studies, using antibodies against biochemically different amyloid fibrils and amyloid-associated proteins, showed reactivity with antibodies only to lambda light chain and serum amyloid P-component. Amino acid sequence analysis of the purified amyloid fibrils extracted from the brain tumor indicates that the amyloid protein is an unusual immunoglobulin lambda light chain, starting at residue five of the variable domain. These fibrils consist of lambda chain fragments of different lengths (10 to 30 kd) very likely arising by polymerization of the amyloid subunit or sequential proteolytic cleavage of the light chain, or both. After exposure to denaturing agents, the 10-kd subunit retains the characteristics of native amyloid fibrils by electron microscopy.