Langerhans cell histiocytosis (LCH) is a rare disorder characterized by high proliferation of Langerhans dendritic cells. LCH is a solitary or multifocal disease that primarily involves bone tissue and often affects children and young men. A 29 years-old Caucasian man was referred to the Oral Surgery Unit of George Eastman Hospital - Umberto I teaching hospital, with third degree mobility of teeth belonging to second, third and fourth quadrant. Panoramic radiograph showed multiple radiolucent areas with well demarcated borders on the right and left site of the mandible and on the left site of the maxilla. Extractions of compromised teeth and biopsy of the osteolytic tissue were performed. The final diagnosis of multisystem Langerhans cell histiocytosis of the soft and hard tissues of the oral cavity was made. The patient was sent to the Hematology department of Umberto I Teaching Hospital of "Sapienza" - University of Rome for the proper treatment. The present case of rare multisystem LCH involving oral hard and soft tissues shows the strong importance of better investigate, with appropriate additional exams, initial shifty symptoms that could lead to a misdiagnosis. Key words:Differential diagnosis, microscopic diagnosis, Langerhans cell histiocytosis.