INTRODUCTION : Erdheim-Chester disease (ECD) is a rare non-Langerhans histiocytosis of unknown etiology, it is characterized by organ infiltration of foamy histiocytes. Diagnosis of ECD involves the analysis of histiocytes in tissue biopsies: these are typically CD68+ CD1a−. These characteristic histiocytes may be found in almost any tissue in cases of ECD. We present an interesting case of ECD that was presented by spontaneous pneumothorax and neurological involvement. CASE: A 18 year old non-smoker woman was referred to our clinic with spontaneous pneumothorax. She had had complaints of exertional dyspnea, cough, back and leg pain for a long time. Physical examination was normal except for operation scars on her chest. Her past medical history included central hypothyroidism and growth retardation. She had no environmental toxic exposure. Pulmonary function test was consistent with restrictive lung disease. Laboratory results were normal (including ANA, ENA profile, VEGF) except for hypoalbuminemia. HRCT scan of chest showed diffuse ground glass opacity and subpleural, parenchymal microcysts (FIGURE). Wedge resection with histopathology and immunohistochemistry reported a histiocytic infiltrate which was positive for CD68 and negative for S100, BRAF V600E mutation. A bone scan showed increased radionuclide uptake of the T12 and L1 vertebrae. Thoracolumbar MRI revealed hemangioma in the T12 vertebrae body. FLAIR and T2 weighted cranial MRI revealed hyperintensities in the bilateral cerebral white matter and pons. MRI of the pituitary showed partial empty sella. Cardiac MRI , Orbital MRI and abdominal tomography were normal. These clinical, radiologic and histopathologic findings were consistent with Erdheim-Chester disease. Patient refused treatment and remained clinically stable for the next 10 months. DISCUSSION: In conclusion, patients with spontaneous pneumothorax, Erdheim-Chester disease should be taken in consideration as a rare clinical manifestation.