The two exceptional patients who presented with multiple LCH lesions containing CXCR4-negative LCH-cells were (1) an 11 y old girl with poly-ostotic LCH who achieved complete remission after chemotherapy and did not show any signs of reactivation within 10 y of follow-up and (2) a 56 y old male who presented with a disseminated form of LCH with poly-ostotic lesions, involvement of LN and possible involvement of lung and liver. Here, CXCR4 is linked to Langerhans cell histiocytosis.