Abstract<\/strong><\/p>\n In recent decades, the low economic performance of European countries has been mainly responsible for the emergence of an economic policy increasingly intended to strengthen the innovative and technology capacity of regions. In particular, the European periphery is lagging behind in the transition to a knowledge driven and eventually service-oriented economy. In a general context of de-industrialization and transition to service economy, and bearing in mind the policy debate at the EU level, the aim of this paper is to analyze the factors driving knowledge-intensive service specialization at the regional level in Italy. Our main research questions here can be summarized as follows: What determines the transition to Services and the specialization in Knowledge-Intensive Services (KIS) in Italy? What are the structural characteristics that may explain the regional variation of employment share in high-knowledge services? Using data on Italian regions over the period 1995-2014 (and spatial panel models as a methodology), the analysis carried out in the paper suggests some considerations: the \u201cmere\u201d (but needed) transition to service activities can be positively associated with R&D Personnel, Tertiary Education, University Attractiveness, Tourism and efficient infrastructure (Railroad). But the transition to Knowledge Intensive Services, supposed to pay higher wages, may deserve a more appropriate and focused public intervention, in view of the fact that it seems to be mainly associated with Public R&D, Tertiary Education and University Attractiveness.<\/p>\n