This is the first report of a patient presenting with rheumatoid factor (RF) positive hypertrophic cranial pachymeningitis (HCP) in association with hypopituitarism and multiple cranial nerve palsies. Our patient developed palsies of the left II and III, bilateral VI and VII, and right IX, X, and XII cranial nerves. A stimulation test showed hypopituitarism due to hypothalamic failure. The patient was seropositive for RF but had no multiple joint pain or deformities. Magnetic resonance imaging (MRI) showed thickened dura of the sellar and parasellar region, hypothalamus, bilateral cavernous sinuses and the tentorium all of which were enhanced by gadolinium (Gd). Treatment with prednisone improved clinical symptoms and MRI findings concomitant with reduction of RF titer. Although the exact mechanism of HCP has not been clearly elucidated, the present case suggests an autoimmune mechanism associated with RF.