Total cellular polyadenylated RNA from a variety of fresh human lymphoma and leukemia cells, characterized by histopathology and certain cell surface markers, was analyzed for the expression of three distinct cellular oncogenes (c-onc genes), c-erbB, c-myc and c-myb by dot-blot hybridization assays. Probes used were molecularly cloned DNA containing the respective oncogene sequence of avian erythroblastosis virus, myelocytomatosis virus (MC29) and myeloblastosis virus. All lymphoma-leukemia cells irrespective of B, T or non-B/non-T lymphocyte lineage expressed the c-erbB locus. This gene was also found to be active in normal peripheral blood lymphocytes and lymphocytes from lymph nodes showing reactive hyperplasia. This observation suggested that c-erbB might be normally involved in cell growth functions since it was not unique to hematopoietic malignancies. In contrast to c-erbB, elevated expressions of c-myc or c-myb were detected in certain neoplasms of B-lymphocytes and some other lymphoproliferative disorders as compared to the majority of the samples tested which showed either low or undetectable levels of these transcripts. An examination of B-cell lymphomas and leukemias in which the majority of the cellular populations expressed either Kappa or lambda surface lg light chain molecules revealed variations in the levels of c-onc transcripts within a morphologic and immunologic subtype. These findings support the notion that, in general, genetic heterogeneity exists in groups of hematopoietic proliferations defined by conventional histopathologic and immunologic criteria. Although with the majority of the specimens there was no obvious correlation between the morphologic cell type of lymphoma/leukemia and the c-onc RNA levels, interestingly two of the three samples diagnosed as chronic lymphocytic leukemia, B-cell type, showed considerably increased transcription of the c-myc gene relative to the other B-cell neoplasms. Thus a class of differentiated B-cell leukemia has been identified in which the molecular mechanisms which affect c-myc gene expression can now be investigated.