Chronic lymphocytic leukemia (CLL) is usually stable over months to years however a small proportion of cases may transform to more aggressive forms. These transformations include diffuse lymphoma (Richter syndrome), prolymphocytic transformation, acute lymphoblastic leukemia and multiple myeloma. There are a variety of techniques to determine whether the transformation represents a clonal evolution of the original CLL or an independent disease. These include cytogenetic analysis, immunoglobulin gene rearrangement by Southern blot analysis, and anti-idiotypic antibodies. While identity can be determined by gene rearrangement and anti-idiotypic antibodies, lack of identity can occur because of somatic mutation within a single clone. Thus, even with optimal techniques it is difficult to definitively exclude lack of identity in some instances. In most cases where transformation has taken place, definitive studies were not performed. In instances where detailed data are available, most do not suggest clonal evolution. Further studies are needed to allow definite conclusions.