Three cases of a morphologically distinctive “sclerosis” of lymph nodes are presented. Two patients experienced recurring lymph node enlargement with associated mild malaise over an extended period. The first patient had unilateral axillary lymph node enlargement, but was asymptomatic and died of chronic obstructive pulmonary disease 17 years later with no evidence of lymph node enlargement at autopsy. Each patient had at least transient hypergammaglobulinemia, one with elevated IgM and IgA, one with elevated IgM, and one (from 1958) not further analyzed. Lymph node biopsies revealed extensive deposition of eosinophilic material in all three patients. Identical changes in lymph nodes have been described in chronic diseases. The eosinophilic material may be related to amyloid, but differs from it histochemically and ultrastructurally. The relationship of this lesion to the few cases reported as amyloidosis presenting as lymph node enlargement is discussed. Malignant lymphoma with sclerosis is the most important consideration in the differential diagnosis.