How regions develop and evolve along their productive and technological path is a central question for scholars and policymakers. From an evolutionary perspective, regions are likely to create and develop new technologies closer to their pre-existing specialisation. In this study, we map the regional European technological knowledge space and investigate regional specialisation's pattern and evolution in the most innovative EU regions. More specifically, we map the technological trajectories of 198 EU regions from 1986 to 2010 using data on 121 patent sectors at the NUTS2 level for the 11 most innovative European countries, including Switzerland and Norway. We maintain that the evolution of technological specialisation depends on three main factors: (i) localised technological change/technological relatedness, (ii) knowledge recombination of related and unrelated technologies, and (iii) regions’ capability of anticipating future technological change in related sectors. Results based on panel-ordered response models, which also account for spatial and technological spillovers, show that the probability of reaching higher states of technological specialisation is mainly driven by localised technological change and anticipated future technological relatedness. In contrast, recombinant innovation contributes to a lower extent.