Skull base osteomyelitis (SBO) is a classically described as a Psuedomonas aeruginosa infection originating from malignant external otitis (MEO). A typical patient with SBO is an eldrly diabetic who presents with temporo-occipital pain and lower cranial nerve palsies. On the other hand, it has been reported that some SBO cases had the atypical nature of the clinical presentation of the disease. We present two cases of SBO with multiple cranial nerve palsies. One case is of a 75 year-old male with diabetes mellitus caused by fluoroquinolone-resitant P. aeruginosa. He was treated by long-term administration of antibiotics and hyperbaric oxygen. The other case is of a 65 year-old male on hemodialysis caused by P. aeruginosa. He was treated by long-term administration of antibiotics.