ABSTRACT: The concept of cross-border regional innovation systems (CBRIS) surfaced in the literature on economic geography through discourses that highlighted the need for broadening innovation systems to cross-border contexts. Since these early discussions, the theoretical backgrounds of CBRIS have been elaborated through notions of geographical scale, proximity and related variety in a range of conceptual papers proposing CBRIS as a comprehensive framework for analysing regional cross-border integration. However, the empirical literature on CBRIS has failed to keep up with the advances in conceptualization. This paper discusses the reasons behind this mismatch, which means that the concept still rests upon and draws policy suggestions based on a thin evidence base. Directions for further research are pointed out by underlining the need for holistic empirical validation of the concept together with the need of understanding how suggested policy measures based on CBRIS reasoning have been implemented in border regions, and their effectiveness in promoting cross-border integration.