Objective: Langerhans' cell histiocytosis (LCH) is an uncommon disease of unknown etiology characterized by uncontrolled proliferation and infiltration of various organs by Langerhans' cells. To our knowledge, this is the first case reporting an association of multisystem LCH with metastasizing adenocarcinoma of the lung. Method: We present the case of a 54-year-old man, heavy smoker, with dispnea, cough, hemoptyses, headache and ataxia, who died shortly after admission to our hospital. On the autopsy, we found tumor in the posterior segment of the right upper pulmonary lobe as well as a right-sided occipito-parietal lesion which penetrated into the right ventricle resulting in internal and external hematocephalus. Histologically and immunohistohemically, the diagnosis of primary lung adenocarcinoma with brain metastasis was made (tumor cells showed positivity for CK 7 and TTF-1 which confirmed the diagnosis). Light microscopic examination of the other organs showed LCH involving the pituitary gland, hypothalamus, spleen, mediastinal lymph nodes, and lungs. Immunohistochemical studies revealed CD68, S-100 and CD1a immunoreactivity within the Langerhans' cells.