Significance A longstanding controversy in neuroscience pertains to differences in human prefrontal cortex (PFC) compared with other primate species; specifically, is human PFC disproportionately large? Distinctively human behavioral capacities related to higher cognition and affect presumably arose from evolutionary modifications since humans and great apes diverged from a common ancestor about 6–8 Mya. Accurate determination of regional differences in the amount of cortical gray and subcortical white matter content in humans, great apes, and Old World monkeys can further our understanding of the link between structure and function of the human brain. Using tissue volume analyses, we show a disproportionately large amount of gray and white matter corresponding to PFC in humans compared with nonhuman primates.