Deficiency of glucose-6-phosphate dehydrogenase (G6PD) is the commonest enzyme deficiency in humans with a wide range of possible clinical manifestations depending on the specific genetic variant in each case. Here we present the case of an 86-year-old male of African descent who acutely developed symptoms of G6PD deficiency immediately after he received methylene blue for treating methemoglobinemia. The contrast between a low SO2 on pulse oximetry and a normal arterial gas sampling raised the possibility of methemoglobinemia. The patient was treated with packed red blood cells and folic acid, and a rapid clinical improvement followed by normalization of the red blood cell count ensued. In view of the patient's advanced age, the lack of a history of similar episodes in the past, and the normal laboratory results during the hemolytic crisis, this case remained a diagnostic challenge for over three months, when a follow-up measure of G6DP activity eventually confirmed the diagnosis. A latent deficiency of G6PD may become clinically manifest under the appropriate triggering conditions even in elderly patients and in the absence of past or current clinical and laboratory evidence of G6PD deficiency.