Cross-border cooperation as a type of interregional interaction is becoming a significant factor in the development of border regions. It can be viewed as a result of intensification of cross-border contacts and greater economic openness of cross-border regions. Thus, the roots of current development are quite easy to pinpoint. However, assessment of the impact of cross-border cooperation on the development of border regions appears to be a research challenge. In this paper, we offer an approach to the assessment of the role of cross-border cooperation in the system of interregional interaction between border regions. We present a system of indices to describe cross-border specialization of interregional interaction in certain fields, namely investment, international trade, tourism, and migration. Cross-border specialization determines the role of cross-border cooperation in regional external relations. The empiric data we have gathered is used to develop and implement a pilot assessment of cross-border spec