The application of polymerase chain reaction (PCR) to cytological material represents a promising, relatively noninvasive approach to clinical molecular genetic analysis. The detection rate of the t(14;18), the most common translocation in B-cell lymphomas, which results in rearrangement of the immunoglobulin heavy chain (IGH) and BCL2 genes, has not been examined in archival cytological smears. We studied 10 cases of lymphoma that showed a cytogenetic t(14;18) in a surgical specimen and for which were available both lymphoma DNA from the same specimen and prior or subsequent archival cytological smears, either FNA or exfoliative, diagnosed as positive for lymphoma. The paired DNA samples, respectively extracted from the archival smears and frozen surgical biopsy tissue, representing clinical intervals of up to 20 mo, were studied in each case by PCR with IGH and BCL2 major breakpoint region primers. In four cases, the same clonotypical PCR product was seen in both samples. In four other cases, neither sample yielded a PCR product--these cases were also negative by Southern blotting using a BCL2 major breakpoint region probe. In one case, the PCR product could only be demonstrated in DNA from frozen tissue. Finally, in one other case, a PCR product was only detected in DNA from archival cytological smears. Thus, the overall concordance of PCR results in the paired DNA samples was 80%. Our findings suggest that, in cases of B-cell lymphoma previously characterized by PCR, the t(14;18) can be detected in archival cytological smears in the majority of cases, thereby providing valuable data regarding the clonal derivation of metachronous lymphoma samples in which only cytological material is obtained.