Richter syndrome (RS) is well known as a secondary high-grade lymphoma, mostly diffuse large B-cell lymphoma (DLBCL) developed in patients with B-cell chronic lymphocytic leukemia (B-CLL). In this review, we describe clinicopathological, histological, immunophenotypical and genetic findings of RS. The patients with RS, regardless of transformation of pre-existing clone or de novo malignant clone, were resistant to conventional combined chemotherapy and died within months of diagnosis. Molecular techniques can provide convincing results for the clonal relationship of RS to pre-existing B-CLL. When RS carries a same rearrangement band or a same sequence as B-CLL by Southern blotting or nucleotide sequence analyses of immunoglobulin heavy and/or light chain genes, it is suggested to that RS transforms from original B-CLL. These analyses have showed that approximately two-thirds of RS cases evolved from a B-CLL clone. How and where does the B-CLL clone evolve to RS? The genetic alteration of transforming B-CLL clone into RS has been addressed. Abnormalities of chromosomes 11 and 14 were most frequently involved in RS, but non-specific. In addition, RS does not include chromosomal translocation between Ig locus and oncogenes or rearrangements of bcl-6 gene, both of which were found in some de novo DLBCL. Several candidates, such as mutation of p53 gene and abnormalities of cyclin dependent kinase inhibitor, have been proposed to play an important role in the transformation of a part of B-CLL. However, there is still uncertainty as to how B-CLL progresses or develops into RS.