Cell lines were established from 15 patients with diffuse histiocytic lymphoma (DHL) of the intermediate grade, diffuse large cell (class G), and high-grade, large cell immunoblastic (class H) types. Immunologic studies indicated that 11 of the 15 DHL cell lines were B cell in origin, 2 were histiocytic, and 2 were null cell. Cytogenetic studies revealed 1 hypodiploid, 11 hyperdiploid, and 3 near-tetraploid cell lines. Chromosome #7 was trisomic in 3 lines, chromosomes #12 in 4 lines, and chromosome #13 in 3 lines. Chromosome #2 was monosomic in 3 lines, chromosome #8 was monosomic in 5 lines, chromosome #14 in 4 lines, and chromosome #22 in 6 cell lines. This is of special interest, as chromosomes #2, #8, #14, and #22 are clearly concerned with rearrangements in Burkitt's lymphoma and immunoglobulin expression. The most common rearrangement in the DHL cell lines involved chromosome #14 at band 14q32. However, in contrast to Burkitt's lymphoma, the pattern of translocation in DHL is between chromosome #14 and usually chromosome #11 or chromosome #18. The 14;18 translocation is not restricted to patients with low-grade follicular, small cleaved cell lymphomas, as has been reported. The 14q+ chromosome is characteristic of lymphoid malignancies in general. It is due, invariably, to a translocation with the breakpoint in band 14q32, which is the locus of the immunoglobulin heavy chain genes. We propose that in each translocation, for example, chromosomes #11 or #18, an oncogene may be transposed onto chromosome #14, and that each 14q+ translocation in DHL represents an event that transposes an oncogene from another chromosome to chromosome #14.