Cytologic evaluation of lymph node fine-needle aspirates and serous effusions is a rapid and useful means for establishing the diagnosis of a variety of lymphoproliferative disorders. However, in some instances, cytologic findings are not sufficient to establish a diagnosis of lymphoma, thus necessitating the use of ancillary procedures, the most frequent of which is immunophenotyping. In this respect, the usefulness of molecular markers, such as clonal immunoglobulin gene rearrangements or chromosomal translocations, have been less well evaluated. Follicular lymphoma constitutes an interesting disease for such a study because these tumors possess characteristic histopathologic features and contain two potential molecular markers, that is, a clonal immunoglobulin gene rearrangement and abcl-2 gene translocation [t (14; 18)]. In the present study, we evaluated, retrospectively, the cytologic material from four lymph node fine-needle aspirates and one pleural effusion of five patients with biopsy-proven follicular lymphoma. In four of the cases, definitive diagnosis of lymphoma had not been possible solely from cytologic evaluation. DNA was isolated from archival air-dried samples present on glass slides and amplified by the polymerase chain reaction (PCR) for detection of either a clonal immunoglobulin heavy chain gene rearrangement orbcl-2 translocation (major breakpoint region). An immunoglobulin heavy-chain gene rearrangement was detected in four of five patients, and two patients had thebcl-2 translocation by PCR. The effusion case was identical by gel electrophoresis with product amplified from a lymph node biopsy of the same patient and DNA extracted directly from fresh pleural effusion cells. The results indicate that PCR may be a useful ancillary procedure in evaluation of patients with follicular lymphoma when the diagnosis cannot be established by morphology alone. This technique does not require any additional cytologic material because the sample present on the original air-dried glass slide can be used as the source of the required DNA.