The authors investigated the structural organization of the bcl-1 locus, a putative oncogene associated with reciprocal chromosomal translocation t(11;14), by Southern blot hybridization analysis and its frequency, distribution, and prognostic significance in a panel of 156 clinically and pathologically well-defined B-cell chronic lymphocytic leukemias (CLLs) and non-Hodgkin's lymphomas (NHLs). The authors detected bcl-1 rearrangements in only 2 of 42 CLLs and 4 of 114 NHLs, specifically 3 of 29 diffuse small lymphocytic and 1 of 10 diffuse small cleaved cell and none of 5 diffuse intermediate lymphocytic, 13 follicular predominantly small cleaved, 17 follicular mixed small cleaved and large cell, 4 diffuse mixed small and large cell, 26 diffuse large cell, and 10 diffuse small noncleaved cell lymphomas. None of seven cases of Rai stage III or IV CLL or seven diffuse large cell lymphomas occurring as Richter's syndrome exhibited bcl-1 rearrangements. In conclusion, the bcl-1 locus rearranges in only about 4% of B-cell CLLs and NHLs, is predominantly rearranged in low-grade B-cell neoplasms, and does not appear to be preferentially associated with those occasional CLLs and low-grade NHLs displaying clinical aggressiveness, advanced clinical stage, or large cell transformation (Richter's syndrome). Therefore the demonstration of bcl-1 rearrangement does not appear to have clinically useful prognostic significance.