Scholars are increasingly interested in innovation in peripheral areas. However, research and policy documents are still often based on a traditional understanding of the core–periphery dichotomy. Here, the peripheralization discourse argues for a broader understanding and highlights the importance of economic, demographic, and political factors as well as knowledge intensity for defining core and peripheral areas. Concerning the latter, the differentiated knowledge base approach provides new insights, as it emphasizes the varying foundations for different kinds of innovations. By combining these hitherto unconnected strands of literature, this paper first develops a conceptual framework for a new regional typology, which considers both the degree of centralization/peripheralization and the prevailing knowledge base. Second, an exploratory analysis applies this framework to the 95 districts of Austria and provides first insights into peripheralization and issues of regional prosperity. The results show that there are indeed many nuances and that regions that are clearly either central or peripheral are the exception. Furthermore, peripheries come in many shades and are not uniform, as often assumed implicitly. Consequently, this paper argues that a tailor-made innovation policy for lagging regions would benefit from the incorporation of the peripheralization discourse. To conclude, it outlines directions for future research.