The familiarity to the subject of any potential stimuli presents one of the major difficulties for the investigation of the self; the separation of effects resulting from familiarity from self-effects being extremely problematic. The aim of this study was thus to investigate the neural distinction between self and familiarity by combining two sets of fMRI data with a meta-analysis. In the first fMRI experiment, regions responding to self/familiarity were investigated using the subject's own name and names of familiar others. These effects were confirmed and extended in a second fMRI experiment using the subject's own name and a stranger's name, as spoken by familiar and unfamiliar voices. Finally, a meta-analysis of self- and familiarity-related studies was conducted. Neural activity in the anterior brain regions, such as the anterior cingulate (ACC) and anterior insula (AI), was found to be specific for self-specific stimuli. In contrast, posterior brain regions, such as the posterior cingulate, were activated by familiar stimuli. Finally, the distinction between anterior and posterior regions for self and familiarity was confirmed by meta-analytic data. This study demonstrates a clear anterior–posterior cortical partition between self-specificity and familiarity. Hum Brain Mapp, 2012. © 2010 Wiley Periodicals, Inc.