Isolated sphenoid sinus disease is a rare, often misdiagnosed condition of the paranasal sinus. If left untreated, it can lead to complications involving pituitary gland, cavernous sinus, neurological and vascular structures nearby. Early recognition and treatment are critical to prevent the progression of the disease. We present a case of a 60-year-old woman with a history of severe left-sided headache, facial pain, diplopia and left lateral rectus palsy. She was initially referred to ophthalmology and rheumatology for possible giant cell arteritis. Magnetic resonance imaging revealed opacification in left sphenoid sinus with cavernous sinus/superior orbital fissure involvement consistent with left sphenoid sinusitis. She was then referred to the ear, nose and throat department and had endoscopic transnasal sphenoidotomy in theatre. Culture results showed and fungal pseudohyphae. She recovered three months later after a course of antibiotics and antifungals. The onset of isolated sphenoid sinus disease is often insidious and the diagnosis of this condition remains a challenge. Magnetic resonance imaging and computed tomography remain the best diagnostic tools to recognise and manage this condition.