Nonrandom chromosomal translocations like the t(14;18), t(8;14), and t(11;14) are found in distinct types of B-cell malignancies. Recent molecular studies concerning their structure and origin showed that many translocations occur in early precursor B cells and may be interpreted as aberrant immunoglobulin gene rearrangements. The available data from in vitro experiments, transgenic mice, and normal human individuals indicate that these translocations are essential but insufficient for full tumorigenesis. The consequent "multi-hit" concept might have important implications for the detection of minimal residual disease using the polymerase chain reaction for these translocations. The strong associations with specific types of lymphomas underline their differences in histogenetic origin. Thus, based on differences in bcl-1 and bcl-2 rearrangements, molecular analysis may help to distinguish follicular lymphoma from diffuse centrocytic lymphoma and chronic lymphocytic leukemia. Furthermore, based on differences in bcl-2 and c-myc rearrangements, subtypes of de novo centroblastic lymphoma can be distinguished that have striking differences in biological behavior, especially nodal versus extranodal presentation. Therefore, future studies will show an increasing clinical relevance of molecular analysis in B-cell neoplasia.