Brain mechanisms for telling lies have been investigated recently using neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography. Although the advent of these techniques has gradually enabled clarification of the functional contributions of the prefrontal cortex in deception with respect to executive function, the specific roles of subregions within the prefrontal cortex and other brain regions responsible for emotional regulation or social interactions during deception are still unclear. Assuming that the processes of falsifying truthful responses and deceiving others are differentially associated with the activities of these regions, we conducted a positron emission tomography experiment with 2 (truth, lie) × 2 (honesty, dishonesty) factorial design. The main effect of falsifying the truthful responses revealed increased brain activity of the left dorsolateral and right anterior prefrontal cortices, supporting the interpretation of previous studies that executive functions are related to making untruthful responses. The main effect of deceiving the interrogator showed activations of the ventromedial prefrontal (medial orbitofrontal) cortex and amygdala, adding new evidence that the brain regions assumed to be responsible for emotional processing or social interaction are active during deceptive behavior similar to that in real-life situations. Further analysis revealed that activity of the right anterior prefrontal cortex showed both effects of deception, indicating that this region has a pivotal role in telling lies. Our results provide clear evidence of functionally dissociable roles of the prefrontal subregions and amygdala for human deception.