This study explores the neurofunctional correlates of the recognition of famous faces in patients with amnestic mild cognitive impairment (aMCI) and healthy controls depending on the genetic risk factor, Apolipoprotein E (ApoE) ε4. An event-related functional magnetic resonance imaging experiment was conducted while participants discriminated between famous and nonfamous faces. We compared the results of 32 healthy controls [17 ApoE ε4 carriers (E4+); 15 noncarriers (E4-)] with those of 30 patients with aMCI (16 E4+; 14 E4-). Despite comparable task performance, patients with aMCI, E4+ showed significantly less activation in a large cortical network including the left parahippocampal gyrus than patients with aMCI E4-. Furthermore, in the aMCI group, we found significantly reduced activation in the left parahippocampal gyrus and posterior cingulate cortex compared with the control group. Our results show that critical regions of the brain show functional decline associated with major risk factors, such as ApoE ε4 allele and neuropsychological signs of aMCI for the development of Alzheimer disease. Importantly, the ApoE genotype seems to influence cortical activation in patients with aMCI and to a lesser degree in healthy controls as well, who are without any cognitive symptoms.