BACKGROUND: Rhinocerebral mucormycosis (RCM) is an uncommon and fatal clinical syndrome resulting from an opportunistic infection caused by a fungus of the order Mucorales in immunocompromized patients. The mortality and morbidity in the patients with intracranial involvement is invariably high, and it was reported that most survivors had early diagnosis and received aggressive treatment. Therefore, we retrospectively reviewed four patients of pathologically confirmed mucormycosis to find out the clues for early diagnosis of RCM and for prediction of fatal intracranial involvement. METHODS: The clinical, radiological features and histo-pathological involvement sites in the patients with intracranial involvement were compared to those without intracranial involvement. RESULTS: All the patients had uncontrolled diabetes and were admitted with orbital involvement. On the precise physical examination, mucosal involvement was found in all patients; three of them in only nasal mucosa and one in oral palatal mucosa. Despite the vigorous antifungal therapy, two patients had intracranial involvement and expired. MRI finding of extensive sphenoid sinusitis adjacent cavernous sinus preceded the intracranial involvement of RCM, which was not found in the patients without intracranial involvement. CONCLUSIONS: Our findings suggest that early observation of oral or nasal mucosal changes might be an important clinical clue for differentiation of RCM from other causes of rhino-oculo-cerebral symptoms in uncontrolled diabetic patients, and that extensive sphenoid sinusitis might be an important radiological feature for predicting the fatal intracranial involvement of RCM.