In almost every large study attempting to characterize non-Hodgkin's lymphomas, there is a small subset of tumors for which the lineage remains poorly defined. The investigators studied a series of 20 hematolymphoid neoplasms that could not be clearly assigned to the B or T cell lineage by phenotypic criteria. Histologically, 12 cases had an appearance suggesting a histiocytic origin, seven cases resembled a pleomorphic immunoblastic lymphoma, and one had a sarcomatoid appearance. By immunologic studies, a variety of B cell, T cell, and monocyte/macrophage markers were expressed on the neoplasms, often with coexpression of markers for different lineages. Twelve cases expressed the Ki-1 antigen. In immunogenotyping studies of T cell receptor (TCR) and immunoglobulin genes, 13 cases showed clonal rearrangements of the beta or gamma TCR gene; one of these cases also had clonal rearrangements of a light chain immunoglobulin gene. Seven cases showed a germline configuration with all combinations of probes and enzymes used. We conclude that a small subset of hematolymphoid neoplasms shows a pattern of diverse immunologic marker expression that does not appear to reflect normal differentiation. However, a majority of these cases contain clonal TCR gene rearrangements, suggesting a frequent relationship to the T lineage.