A major issue in modern ecology is to understand how ecological complexity at broad scales is regulated by mechanisms operating at the organismic level. What specific underlying processes are essential for a macroecological pattern to emerge? Here, we analyze the analytical predictions of a general model suitable for describing the spatial biodiversity similarity in river ecosystems, and benchmark them against the empirical occurrence data of freshwater fish species collected in the Mississippi-Missouri river system. Encapsulating immigration, emigration, and stochastic noise, and without resorting to species abundance data, the model is able to reproduce the observed probability distribution of the Jaccard similarity index at any given distance. In addition to providing an excellent agreement with the empirical data, this approach accounts for heterogeneities of different subbasins, suggesting a strong dependence of biodiversity similarity on their respective climates. Strikingly, the model can also predict the actual probability distribution of the Jaccard similarity index for any distance when considering just a relatively small sample. The proposed framework supports the notion that simplified macroecological models are capable of predicting fundamental patterns-a theme at the heart of modern community ecology. macroecology ͉ river networks ͉ Jaccard index ͉ average annual runoff production ͉ Mississippi-Missouri basin T he fundamental mechanisms that underlie emergent biodiversity patterns are the fabric of the large canvas of ecological complexity (1-5), whose functioning across spatial and temporal scales is still challenging modern ecologists (6, 7).River ecosystems, like tropical forests, constitute an invaluable source of species diversity whose study can shed light on these puzzling issues (8), and whose insights will in turn resonate in the conservation biology of freshwater fauna suffering extinction rates comparable to the species decline in tropical rainforests (9). Riverine ecology has recognized the importance of geomorphology for biodiversity (10): on the one hand, ecologists have investigated the role of branches (11-13) and riparian zones (14) as primary habitats as well as the importance of tributaries (15) in sculpting species diversity (16, 17); on the other hand, theoretical studies have looked into possible implications of dendritic networks (18) on population persistence (19), species richness, and spatial turnover (20). Recent advances have also pointed out that simplifying neutral assumptions can reproduce important macroecological patterns in such dendritic structures (21).Indeed, despite the fact that biodiversity similarity among habitat patches is crucial to dispersal, speciation, and adaptation to climate diversity at large scales (22) and can also be related to species richness (23, 24), it is not well understood yet. Here, we develop an analytical model suggesting that essential features of biodiversity similarity in river ecosystems may be captured by using only the occurrence...