Reeler mice exhibit loss of the signaling protein Reelin (Reln) which affects radial pyramidal neuron migration and results in cortical layer malformation. During cortical development Eph receptor/ephrin ligand (Eph/Efn) cell-cell interactions are important for neuronal migration, axonal/dendritic growth, synaptogenesis, and pruning. Recently it has been claimed that Ephb/Efnb and Reln pathways interact genetically and layering defects in triple Efnb1;2;3−/− mutants and Efnb3−/−;Reln+/− compound mice are similar to those present in reeler. Here we demonstrate that contrary to this previous report the compound mutant Efnb3−/−;Reln+/− as well as the triple mutant Efnb1;2;3−/− do not show defects of cortical layering or elevated Dab1 levels. While protein-protein interactions between Efnbs and Reln have been confirmed, they do not affect the radial positioning of migrating neocortical pyramidal neurons.