The medial prefrontal cortex (MPFC) appears to play a prominent role in two fundamental aspects of social cognition, that is, self-referential processing and perspective taking. However, it is currently unclear whether the same or different regions of the MPFC mediate these two interdependent processes. This functional magnetic resonance imaging study sought to clarify the issue by manipulating both dimensions in a factorial design. Participants judged the extent to which trait adjectives described their own personality (e.g., “Are you sociable?”) or the personality of a close friend (e.g., “Is Caroline sociable?”) and were also asked to put themselves in the place of their friend (i.e., to take a third-person perspective) and estimate how this person would judge the adjectives, with the target of the judgments again being either the self (e.g., “According to Caroline, are you sociable?”) or the other person (e.g., “According to Caroline, is she sociable?”). We found that self-referential processing (i.e., judgments targeting the self vs. the other person) yielded activation in the ventral and dorsal anterior MPFC, whereas perspective taking (i.e., adopting the other person's perspective, rather than one's own, when making judgments) resulted in activation in the posterior dorsal MPFC; the interaction between the two dimensions yielded activation in the left dorsal MPFC. These findings show that self-referential processing and perspective taking recruit distinct regions of the MPFC and suggest that the left dorsal MPFC may be involved in decoupling one's own from other people's perspectives on the self.