Chromosomal abnormalities play a central role in the pathogenesis, diagnosis, and treatment monitoring of many hematologic disorders. Cytogenetic studies on bone marrow may be helpful in many malignant hematologic disorders as the observation of a chromosomally abnormal clone may be consistent with a neoplastic process. Certain chromosome abnormalities may help classify a malignancy. As examples, the Philadelphia (Ph) chromosome, also referred to as der(22)t(9;22)(q34;q11.2), is usually indicative of chronic myeloid leukemia (CML) or acute leukemia; t(8;21)(q22;q22) defines a specific subset of patients with acute myeloid leukemia; and t(8;14)(q24.1;q32) is associated with Burkitt lymphoma. Cytogenetic studies are also used to monitor patients with hematologic neoplasia and may identify disease progression, such as the onset of blast crisis in CML, which is often characterized by trisomy 8, isochromosome 17q, and multiple Ph chromosomes. Conventional chromosome studies of B-cell disorders are not always successful because B lymphocytes do not proliferate well in cell culture. The agent CpG 7909 (CpG) is a synthetic oligodeoxynucleotide that binds to the Toll-like receptor 9 (TLR9) present on B cells, causing B-cell activation. In the laboratory setting, CpG may be used as a mitogen to stimulate B cells in patient specimens, thus allowing identification of chromosome abnormalities. CpG stimulation reveals an abnormal karyotype in approximately 80% of patients with chronic lymphocytic leukemia, and the karyotype is complex in 20% to 25% of cases. Several studies have reported that increased genetic complexity revealed by CpG-stimulated chromosome studies confers a less favorable time to first treatment, treatment response, and overall survival.