Isolated sphenoid sinusitis is a rare clinical entity which may cause disturbing headache not only in the sphenoid sinus area but the pain may refer to occipital, frontal, temporal area, or vertex, or may cause retroorbital pain. The diagnosis of isolated sphenoid sinusitis as a potential cause of headache is often missed or delayed due to the nonspecific presentation and needs to be considered when a patient presents with atypical headaches. A normal nasal endoscopic examination does not exclude sphenoid sinus disease. The diagnosis of isolated sphenoid sinus disease is often made radiologically, as symptoms and signs are nonspecific. Headaches which are not responding to conservative treatment should be referred to tertiary settings for further assessment Mycetoma should be kept in mind in the differential diagnosis.