The neuroimaging of Langerhans cell histiocytosis (LCH), in most of the cases, is nonspecific and can vary depending on the location, especially as shown on magnetic resonance imaging (MRI). In the absence of a clinical history of LCH, isolated central nervous system (CNS) lesion presents a diagnostic challenge. LCH should be considered in the differential diagnosis of craniofacial tumors and neurodegenerative (ND) lesions of the brain. MRI is the modality of choice for investigating the CNS-LCH. Long-term follow-up with MRI is indicated in patients with ND-LCH. This retrospective study provides a comprehensive description of the spectrum of neuroimaging findings in patients with LCH, the underlying neuropathology, and follow-up study of the disease.