IgG4-related sclerosing disease is a recently recognized syndrome characterized by mass-forming lesions in exocrine glands or extranodal tissues due to lymphoplasmacytic infiltrates and sclerosis, a raised serum IgG4 level and increased IgG4+ plasma cells in the involved tissues. We report the morphologic features of the enlarged regional (n=3) and nonregional lymph nodes (n=3) in patients with this syndrome. The patients presented with autoimmune pancreatitis, lymphoplasmacytic sclerosing cholangitis, chronic sclerosing dacryoadenitis, or chronic sclerosing sialadenitis. The histologic features of the lymph nodes could be categorized into 3 patterns: Castleman diseaselike, follicular hyperplasia, and interfollicular expansion by immunoblasts and plasma cells. The percentage of IgG4+/IgG+ plasma cells was markedly elevated (mean 62% vs. 9.9% in 54 control lymph nodes comprising a wide variety of reactive conditions). We also report 6 cases of primary lymphadenopathy characterized by increased IgG4+/IgG+plasma cells (mean 58%). These cases share many clinical and pathologic similarities with IgG4-related sclerosing disease. In fact, 2 of these patients developed lymphoplasmacytic sclerosing cholangitis or lacrimal and submandibular gland involvement during the clinical course. These cases therefore probably represent primary lymph node manifestation of the disease. The importance of recognition of the lymphadenopathic form of IgG4-related sclerosing disease lies in the remarkable response to steroid therapy, and the potential of mistaking the disease for lymphoma either clinically or histologically.