Langerhans cell histiocytosis (LCH) is an inflammatory neoplasia of myeloid precursor cells driven by mutations in the mitogen-activated protein kinase (MAPK) pathway. It can present as single or multisystem LCH. It occurs in 0.5-5.4 per million people. While it can occur at any age, it is more common in children, predominantly males, under the age of 4 years. The unifocal single system variety is the most prevalent and least aggressive presentation, making up to 70% of cases. It can affect bone (80%), lymph nodes (5-10%) or lungs (15%). The mandible and sphenoid are the least common locations; therefore, when present, it could be easily mistaken for a variety of pathologies. Depending on the clinical features, treatment can range from simple observation to chemotherapy and/or radiation. We present 2 cases of unifocal single system LCH located at the mandible and skull base, and describe the diagnostic work up and treatment.