IgM monoclonal gammopathy of undetermined significance (IgM MGUS) and Waldenström macroglobulinemia (WM) are sometimes clinically difficult to distinguish. In our previous study, deletion of the long arm of chromosome 6 (6q) was found in about half of WM patients. To further clarify the area of minimal deletion at 6q (6q-) and to address the issue of whether 6q- occurs in IgM MGUS, 12 IgM MGUS and 38 WM patients were studied by fluorescence in situ hybridization using probes targeting different chromosomal segments of 6q. No 6q deletions were found in IgM MGUS samples. Of 38 successfully studied WM patients, 21 (55%) showed a deletion of 6q. The area of minimal deletion was between 6q23 and 6q24.3, but the deletion usually encompassed a large fragment of the 6q arm. These results indicate that 6q- can distinguish WM from IgM MGUS and is likely to be a secondary event.