Lymphoplasmacytic lymphoma (LPL) is a small B-cell neoplasm with plasmacytic differentiation that does not fulfill the criteria for any other type of B-cell leukemia or lymphoma. In many cases, LPL is associated with Waldenström macroglobulinemia (WM), although WM may also be associated with other types of lymphoma. Recent studies have demonstrated that del(6q) is the most common structural abnormality in patients with bone marrow-based LPL. It is unknown whether del(6q) might also be associated with nodal LPL. We, therefore, examined 10 well-characterized LPL involving lymph nodes or other extramedullary tissues for del(6q) using paraffin section interphase fluorescence in situ hybridization (FISH). Dual-color FISH was performed using a chromosome 6 centromere probe (CEP6) and a probe for 6q21 (RP11-91C23). The latter probe has previously been reported as deleted in up to 63% of cases of bone marrow-based LPL. In contrast, no nuclei containing a del(6q) pattern were identified in any case of extramedullary LPL examined in this study, and 89-98.5% of nuclei contained a normal signal pattern. These results indicate that del(6q) is at least uncommon in nodal LPL, and cannot be employed as a diagnostic marker to identify this type of lymphoma. Furthermore, these findings suggest that nodal LPL and bone marrow-based cases of LPL may be associated with different cytogenetic findings.