There has been no agreement as to whether the prefrontal cortex is especially enlarged in the human brain. To answer this question, we analyzed the only two datasets that provide information on total prefrontal cortex volume based on cytoarchitectonic criteria. One delineated the prefrontal cortex proper on the basis of cytoarchitectonic criteria; the other used a proxy of the prefrontal cortex based on a cytoarchitectonic delineation of the frontal lobe. To investigate whether all cortical association areas, including the prefrontal cortex, are enlarged in the human brain, we scaled the different areas to a common reference, the primary visual cortex. To investigate whether the prefrontal cortex is more enlarged than other association areas, we scaled it relative to its inputs from and outputs to other nonprimary areas. We carried out separate regression analyses using different data samples as a predictive baseline group: data for monkeys alone informs us on whether great apes are different from monkeys; data for all non-human anthropoids, including great apes, informs us on whether humans are different from all other primates. The analyses show that the value for the human prefrontal cortex is greater than expected, and that this is true even when data for the great apes are included in the analysis. They also show that the chimpanzee prefrontal cortex is greater than expected for a monkey with a similar sized cortex. We discuss possible functional consequences.