During the last decades, the cross-border industrial area of "Longwy-Athus-Rodange" (located between France, Belgium and Luxembourg along the Chiers valley), has undergone profound economic and spatial changes. During the golden age of the mining and steel industry the area experienced urban growth. Changes in the mode of production from the mid 1960s, however, signified the beginning of a structural crisis in the steel industry. As a response, the three national governments agreed on a common strategy in order to boost the economy in the Chiers valley. However, the results of this policy were not up to the expectations and the conditions of urban growth have changed since then. The aim of this study is to examine the evolution of interactions between cities and industries in the cross-border area of "Longwy-Athus-Rodange" using a chronological approach. Our analysis reveals an increasing spatial differentiation along two scales: firstly, between cities on each side of the national borders and secondly, between the industrial areas and the emerging metropolis of Luxembourg City transforming the mono-industrial area into a periphery. This also suggests that national borders play an even more powerful role of differentiation than in the industrial period despite the increasing integration of the European Union.