Langerhans cell histiocytosis (LCH) has previously been reported in association with other malignancies. The pathogenesis of LCH and its relationship to other malignancies is poorly understood. We present a novel case of a child who developed an LCH bone lesion while receiving a Phase I protocol therapy with oral fenretinide/Lym-X-Sorb (4-HPR/LXS) powder for neuroblastoma.