The study aims at advancing our understanding of the regional structure of knowledge production in European regions. To this aim, the paper introduces two novelties: first, the researchers developed a classification of European regions that, while still being compatible with EUROSTAT-NUTS, is more adapted to the distribution of knowledge activities and, notably, provides for a better delineation of metropolitan regions and knowledge hubs. Second, building on data provided by the RISIS-KNOWMAK project, the researchers are able to analyze knowledge production through its different sages, from human resources training to S&T production until transfer to spin-off companies. Preliminary results confirm previous insights on the concentration of knowledge production in large metropolitan areas, but also display significant differences between dimensions of knowledge production in the regional hierarchy; they also highlight the important role of middle-sized ‘knowledge hubs’ characterized by a high intensity.