OBJECTIVES: IgG4-related disease is a recently recognized condition that can be associated with lymphadenopathy, with several histologic patterns and increased absolute number and ratio of immunoglobulin G4 (IgG4)-positive plasma cells. However, these findings are considered to be not exclusively specific for IgG4-related disease. METHODS: The occurrence of the histologic patterns reported in patients with isolated lymphadenopathy was studied and correlated with the clinical presentation to determine their predictive value for IgG4-related lymphadenopathy. RESULTS: We found cases meeting all histologic criteria for IgG4-related lymphadenopathy, without clinical signs of IgG4-related disease. The only pattern that was not seen in this series was an inflammatory pseudotumor-like picture. CONCLUSION: Without a clinical suspicion of IgG4-related disease, these morphologic patterns and high numbers of IgG4-positive plasma cells should be interpreted with care to avoid an erroneous diagnosis of IgG4-related disease.