Genotypic analyses were performed in six primary cutaneous lymphomas whose lineage could not be assessed on the basis of histologic and phenotypic data. By immunophenotyping, these neoplasms expressed leukocyte common antigen and HLA-DR but did not show consistent immunostaining for B-cell or T-cell differentiation antigens. Expression of nonspecific histiocytic markers such as lysozyme and alpha 1-antitrypsin was found in three cases. By genotyping, three cases retained a germline configuration and immunoglobulin gene rearrangement was observed in one case, T-cell receptor gene rearrangement was found in one case, and both types of rearrangements in one case. Of the three patients in whom gene rearrangements were noted, two rapidly died and the other patient, with a dual genotype, is still alive 15 years after diagnosis. The three patients without gene rearrangements are alive and well after a mean follow-up of 2.5 years. It appears that cutaneous lymphomas with an uncertain phenotype include at least some cases of authentic B-cell or T-cell lymphomas. The germline configuration that we observed in cases with a chronic course remains difficult to explain. It may be related to a low malignancy form of histiocytic lymphoma, an atypical polyclonal hyperplasia, or even a low-grade lymphoma arising from a primitive cell without established commitment to either B- or T-cell lineage.