Association between trisomy 8 and myeloid disorders/malignancies has been well documented. We report on two patients with a known history of B-cell chronic lymphocytic leukemia (B-CLL) with bone marrow involvement. In addition to the classic B-CLL cytogenetic abnormalities in one of the patients, both showed a trisomy 8 clone in their bone marrow specimens. Using a BioView Duet automated scanning system, which allowed us to combine histology with fluorescence in situ hybridization, we showed that the trisomy 8 clone was restricted to the myeloid lineage. We believe that this finding signifies the development of myelodysplastic syndrome (de novo or therapy related), rather than progression of B-CLL with the occurrence of a new clone, and that in general, it has implications for the finding of trisomy 8 in CLL.