Topical benzocaine and lidocaine are widely used in general anesthesia to minimize the stimulation by awake intubation and in very rare occasion they may induce methemoglobinemia. Although this complication is uncommon, it may be potentially lethal. Here we report a 29-year-old female who was scheduled to receive correction of malocclusion and developed acute methemoglobinemia soon after induction of general anesthesia. Three weeks ago, she had received open reduction for fracture of mandible with intermaxillary fixation under general anesthesia, for which awake fiberoptic intubation was smoothly performed after premedication with 2% topical lidocaine and intravenous fentanyl. This time, trachomucosal block with 4 mL of 4% topical lidocaine and spray of 20% topical benzocaine over the oral cavity and nostrils were carried out before intubation. Awake blind intubation was performed because she could not open her mouth for more than 1 cm. A 6.5 mm-sized nasal endotracheal tube was smoothly placed in first attempt. About 10 min later, an unexplained cyanosis occurred and SpO2 fell to about 70%. Based on a high oxygen tension by arterial blood gas analysis (PaO2) with a contradictory fall of oxygen saturation by pulse oximetry (SpO2), acute methemoglobinemia was highly suspected. The diagnosis was confirmed by multiple-wavelength CO-oximetry. The methemoglobinemia was resolved gradually after methylene blue was given. In conclusion, we must always take the possibility of methemoglobinemia into consideration for differential diagnosis in case of unexplained cyanosis, particularly when patients have prior exposure to methemoglobin-inducing agents.