Recent neuroimaging studies have shown the importance of the prefrontal and anterior cingulate cortices in deception. However, little is known about the role of each of these regions during deception. Using positron emission tomography (PET), we measured brain activation while participants told truths or lies about two types of real-world events: experienced and unexperienced. The imaging data revealed that activity of the dorsolateral, ventrolateral and medial prefrontal cortices was commonly associated with both types of deception (pretending to know and pretending not to know), whereas activity of the anterior cingulate cortex (ACC) was only associated with pretending not to know. Regional cerebral blood flow (rCBF) increase in the ACC was positively correlated with that in the dorsolateral prefrontal cortex only during pretending not to know. These results suggest that the lateral and medial prefrontal cortices have general roles in deception, whereas the ACC contributes specifically to pretending not to know.