An 84-year-old female presenting with proptosis and hyperviscosity syndrome was found to have Waldenström macroglobulinemia. Karyotypic analysis showed structural chromosomal abnormalities involving both homologous chromosomes 6 with a deleted 6q at q21-q23 and a complex three-break rearrangement in the t(6;13;21)?(q21;q14;q11). A literature review suggests that deletions of chromosome 6 at 6q21 are associated with lymphoplasmacytoid differentiation and IgM production in B-cell chronic lymphoproliferative disorders.