The coincidence of T-cell acute lymphoblastic leukemia (T-ALL) and histiocytic disorders, including hemophagocytic lymphohistiocytosis (T-ALL/HLH) and Langerhans cell histiocytosis (T-ALL/LCH), is very seldom and is usually associated with a dismal prognosis. Retrospective statistical analysis of all T-ALL patients, who have been registered in the BFM-ALL trials from 1981 - 2001 and who have subsequently developed a LCH/HLH, in order to identify any common risk factors pre-disposing to the synchronous occurrence of both disorders. Six out of 971 T-ALL patients had either HLH or LCH ( approximately 0.03% of treated T-ALL/year). The mean age at diagnosis of T-ALL/HLH/LCH was significantly lower than in the remaining T-ALL group (4.05 +/- 0.59 vs 8.82 +/- 0.14 years; p = 0.000). The mean initial leukocyte count was higher than in the non-HLH/LCH group (270,700 +/- 60,677 microl(-1) vs 134,141 +/- 5,663 microl(-1); p = 0.074). No hemophagocytosis was seen in the initial bone marrow (BM) smears. Five of 6 patients obtained a good prednisone response (GPR) at day 8 in peripheral blood with <5% blasts at day 15 in BM and all cases were in complete remission (CR) at day 33. The mean time until development of the histiocytosis was 17.95 months (range 2.5 - 33 months). Four patients developed a HLH and 2 a LCH. All patients with HLH showed a multi-organ involvement, while the LCH patients had only local disease. Only the LCH patients survived, while all patients with HLH died. The authors recommend a close follow-up for at least 3 years after diagnosis in younger T-ALL patients with high initial leukocyte count.