The DSM-5 explicitly states that the neural system model of specific phobia is centered on the amygdala. However, this hypothesis is predominantly supported by human studies on animal phobia, whereas visual cuing of other specific phobias, such as dental fear, do not consistently show amygdala activation. Considering that fear of anticipated pain is one of the best predictors of dental phobia, the current study investigated neural and autonomic activity of pain anticipation in individuals varying in the degree of fear of dental pain. Functional brain activity (fMRI) was measured in women (n = 31) selected to vary in the degree of self-reported fear of dental pain when under the threat of shock, in which one color signaled the possibility of receiving a painful electric shock and another color signaled safety. Enhanced functional activity during threat, compared to safety, was found in regions including anterior insula and anterior/mid cingulate cortex. Importantly, threat reactivity in the anterior insula increased as reported fear of pain increased and further predicted skin conductance changes during pain anticipation. The sample was comprised of women. Individual differences in fear of pain vary with activation in the anterior insula, rather than with the amygdala, indicating that fear is not uniquely associated with amygdala activation. Whereas coping techniques such as emotion regulation have been found to vary with activation in a frontal-amygdala circuit when confronted with visual cues, precision psychiatry may need to target specific brain circuits to diagnose and treat different types of specific phobia. Copyright © 2020. Published by Elsevier B.V.