Hypertrophic cranial pachymeningitis (HCP) is an uncommon disorder with few studies correlating clinical, imaging and histopathological features. The aim of this study was to describe clinical and laboratory observations and therapeutic options of patients with HCP. Eleven patients with HCP (M:F 6:5; age range, 23-52 years) were evaluated over 10 years. Etiology was ascertained by MRI and laboratory tests and confirmed by biopsy of meninges and/or brain (7), nasal mucosa (1), mediastinal lymph node (1), muscle (2) or conjunctiva (2). Salient clinical features were headache (7), multiple cranial neuropathies (8), visual disturbances (6), seizures (2) and hemiparesis (2). Abnormal tests included: rapid erythrocyte sedimentation rate (3), positive serum venereal disease testing (1), chest CT abnormalities (4/6) and positive Mantoux test (2/5). Cerebrospinal fluid changes (10/11) revealed the following: cell count 0-47/mm(3); protein 14-95 mg/mL; and glucose of 44-79 mg/mL. Contrast MRI revealed a variable extent of thickened dura mater in all patients. Histopathology (n=11) confirmed chronic inflammation (100%) and provided specific etiology in six (vasculitis [2], sarcoidosis [2], tuberculosis [1], Wegener's granulomatosis [1]). Treatment included steroids only (4), anti-tubercular therapy with steroids (5), penicillin (1) and cyclophosphamide and plasmapheresis (1). During follow-up (27.0+/-26.3 months) there was significant recovery (9/9). On serial imaging (4), the lesion remained the same in three and resolved partially in one patient. HCP, despite frequently posing diagnostic and therapeutic challenges, has favorable outcome when treated appropriately.