The DEL cell line isolated from a patient who died of malignant histiocytosis exhibits a reciprocal chromosomal translocation t(5;6) (5q35;6p21). The cells were analyzed for lg(Jh), TCR β‐gene rearrangements and proto‐oncogene expression pattern, using a panel of molecularly cloned probes that in cluded c‐fms, c‐myc, c‐myb, c‐pim, c‐fos, N‐myc, c‐sis, c‐fgr as well as the virally derived probes v‐ki‐ras and v‐src. Consistent levels of expression of c‐fms, c‐myc, c‐myb, c‐ki‐ras and c‐fgr were identified in cells from several in vitro passages as well as from the heterotransplanted tumors in nude mice. Transcripts homologous to the c‐fos, c‐src and c‐sis were not observed. Southern blot study of DNA showed that the banding pattern of the screened proto‐oncogenes was not altered. Furthermore, Southern blot analysis demonstrated monoallelic immunoglobulin heavy chain (IgJh) rearrangement but a normal germ‐line configuration of the K light chain and TCR β‐genes. These results appear to imply that a T‐ or B‐cell origin can be eliminated and that several activated protooncogenes, usually expressed in immature MPS cells (c‐fms) and myeloblastic cells (c‐fgr), may be implicated in the proliferative activity of the DEL cell line, the stem of which may be a primitive, ancestral myelomonocytic cell. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company