What makes the human mind unique? What is the sapient mind made of? The turn of the 21st century has seen a new era in the cognitive and brain sciences that allows us to address the age old question of what it means to be human from a whole new range of different perspectives. Our knowledge of the workings of the human brain increases day by day and so does our understanding of the extended, distributed, embodied and culturally mediated character of the human mind. This Theme Issue attempts a cross-disciplinary coalition between archaeology, anthropology and neuroscience, aiming at a new integrative approach to the study of human cognitive becoming (both before and most importantly after the so-called speciation phase). Focusing on the interface between brain and culture, this Issue covers topics ranging from the unique ability of the human mind to manufacture and use a wide range of tools, to the possible role of material culture and joint action in the shaping of human self-awareness and agency. Moreover, the human capacities to imagine, learn from instruction, accumulate and transmit cultural knowledge are examined in the light of new findings from social neuroscience. Finally, some of the most significant manifestations of human social intelligence such as symbolism, religion and value are explored placed against their possible cultural and neurological foundation.