jats:pIn recent years, the question of “difference” has become a central feature of public debate and social concern, especially in the context of transnational migration. The underlying question that we attempt to answer in this article is: how can we talk about difference without reinforcing prejudice? Starting from the observation that perceptions and representations of difference have an impact on the way that individuals and groups interact with each other in increasingly diverse urban environments, we argue that a systemic approach to the analysis of intercultural situations gives us a unique window into emerging discourses and evolving norms about difference. After a brief historical overview of debates surrounding cross-cultural comparison in anthropology, we consider how various fields outside of anthropology have drawn inspiration from anthropology in order to gain a deeper understanding of intercultural dynamics in various professional settings. This article also examines several anthropological concepts that have been used as tools to theorize cross-cultural comparison, and how participants in a new research methodology use the systemic notion of “cultural variables” to resolve the basic paradox underlying pluralist philosophy and practice.</jats:p>