Langerhans cell histiocytosis (LCH) and malignancy occurring in the same individual is unusual and has generally been the subject of isolated case reports. To better define the occurrence of these events a registry of cases with synchronous or asynchronous LCH and malignancy was developed with the cooperation of the Histiocyte Society. In 1991 the Histiocyte Society surveyed its members requesting information on cases in which LCH was associated with malignancy. The questionnaire was mailed to all members of the society and specifically requested information on the clinical and laboratory features of the cases, disease evolution, and response to therapy. Retrospective reporting was allowed. With this initial data, an ongoing registry of LCH patients with associated malignancy was begun of such cases, including evolution and response to therapy. Twenty-seven patients were enrolled during the first year of registry, of whom 4 patients had the association of LCH with a malignant lymphoma and 10 cases had an association of LCH with other types of solid tumor. The remaining 13 patients had the association of LCH with acute leukemia. In five cases, LCH was associated with acute lymphoblastic leukemia FAB L1 (ALL). In four cases the ALL preceded the LCH by 6 months to 1 year. In four of five patients the LCH was localized; in two instances the LCH was treated with chemotherapy. In all cases the leukemia was treated according to local standard ALL protocols and in one case autologous bone marrow transplantation (ABMT) was performed at relapse. Three patients are free of leukemia, one of whom has persistent localized LCH of the skin. Two patients died of the ALL, one of whom was free of the LCH at the time of death. In eight instances LCH was reported in association with acute myeloid leukemia (AML). Six of these patients had a generalized form of LCH. In seven the diagnosis of LCH preceded the diagnosis of leukemia by more than 2 years (median 4 years). In the remaining patient both diagnoses were made concurrently. In all seven cases in whom LCH was the initial diagnosis the treatment consisted of chemotherapy and/or radiotherapy. Seven patients died from the AML, five without evidence of LCH. The temporal patterns of the LCH-ALL and LCH-AML associations are distinct with ALL usually preceding the diagnosis of LCH and AML succeeding it.(ABSTRACT TRUNCATED AT 400 WORDS)