B cell chronic lymphocytic leukemia (CLL) lacks a consistent genetic abnormality. However, immunoglobulin V(H) gene segment mutation analysis has provided insights into the pathogenesis of these diseases and allowed the development of powerful prognostic markers. Immunoglobulin gene chromosomal translocations are rare in CLL and involve a distinct subset of genes including BCL3, BCL11A and CCND2. BCL2 translocations in CLL appear to arise via a different mechanism from comparable translocations seen in B cell non-Hodgkin lymphoma.