The capability to foster metacognitive evaluations (MEs) of oneself and others represents a major component of conscious awareness. Separate emerging lines of brain activation research examining ME have converged on the medial prefrontal cortex as a common finding. The current functional magnetic resonance imaging (fMRI) study utilized a task that directly compared ME associated with two referentially discrete targets: oneself and a significant other (e.g., close friend or relative). Nineteen healthy young adult participants (mean age 24; 9 female, 10 male) were required to make yes/no decisions based on individually presented trait adjectives across two separate referential conditions and a nonreferential control condition: self-evaluation (SE), significant other-evaluation (OE), and semantic positivity-evaluation (SPE), respectively. Results of random-effects group analyses indicated a common area of medial prefrontal activation during the ME conditions of self- and other-evaluation versus the baseline semantic positivity-evaluation condition. A direct comparison of brain activation between the self and other evaluative conditions revealed a right dorsolateral prefrontal response that was significantly more active when making evaluations about the self. The present study extends upon the prior findings of separate research domains by directly comparing the cerebral response to ME about the self and others, and finding right PFC activation increases as a function of self-relevance.