The authors propose a paradigm shift in the investigation of the self. Synthesizing neuroimaging results from studies investigating the self, the authors first demonstrate that self-relatedness evaluation involves a wide cerebral network, labeled E-network, comprising the medial prefrontal cortex, precuneus, temporoparietal junction, and temporal poles. They further show that this E-network is also recruited during resting state, others' mind reading, memory recall, and reasoning. According to these data, (a) the profile of activation of the E-network demonstrates no preference for the self, and (b) the authors suggest that activity in this network can be explained by the involvement of cognitive processes common to all the tasks recruiting it: inferential processing and memory recall. On this basis, they conclude that standard ways to tackle the self by considering self-evaluation do not target the self in its specificity. Instead, they argue that self-specificity characterizes the subjective perspective, which is not intrinsically self-evaluative but rather relates any represented object to the representing subject. They further propose that such self-specific subject-object relation is anchored to the sensorimotor integration of efference with reafference (i.e., the motor command of the subject's action and its sensory consequence in the external world). (Contains 2 figures, 3 tables and 8 footnotes.)