Rosai-Dorfman disease is a lymphoproliferative disease that rarely involves the central nervous system. A 32-year-old patient with an extensive process involving the petroclival region, cavernous sinuses, suprasellar region, anterior cranial fossa, paranasal sinuses, nasal cavity and spinal cord is reported. Sinus histiocytosis with massive lymphadenopathy lesions may be dural-based and located in the skull base. As these lesions may clinically and radiologically mimic meningiomas as well as other disorders, Rosai-Dorfman disease should be included in the differential diagnosis of extensive lesions involving the intracranial and spinal compartments along with meningiomatosis and inflammatory diseases. The individual management of Rosai-Dorfman disease may be challenging due to diffuse involvement of neurovascular structures at the skull base.