OBJECTIVE To evaluate the role of cytogenetic study and interphase FISH analysis in differential diagnosis of patients with clinical and/or cytological diagnosis as lymphoma or "suspicious for lymphoma". METHODS Routine histology, immunohistochemistry, cytogenetics and interphase FISH studies were used to assess 223 cases with superficial lymph nodes of not less than 1. 5 cm in diameter. The probe used in the interphase FISH assays is the Vysis' LSI IGH Dual Color, Break Apart Rearrangement Probe. RESULTS Based on these studies, forty-four patients were diagnosed as Hodgkin's lymphomas ( HL) , 162 as Non-Hodgkin's lymphomas ( NHL) , 11 with benign diseases and 4 as other malignancies, while the remaining 2 cases were discarded due to tissue necrosis. Using interphase FISH, abnormalities of immunoglobulin heavy chain gene (IGH) were detected in 6/44 (13.6%) and 83/162 (51.2%) in the HIL and NHL cases, respectively, while none was observed in 11 cases with a benign disease (P <0. 001). Combining cytogenetics and FISH studies, the detection rates for HL and NHL cases then increased to 15.9% and 77. 8%, respectively, otherwise, 3 of whom could not have made definite diagnosis. CONCLUSIONS Interphase FISH assay is a rapid and sensitive tool for detecting IGH abnormalities. Both cytogenetics and interphase FISH analyses may play a significant role in diagnosis of lymphomas.