One model for dendritic protein sorting in neurons is based on parallels with basolateral targeting in Madin-Darby Canine Kidney (MDCK) epithelial cells. The goal of this study was to further evaluate this model by analyzing the neuronal targeting of several proteins that contain well-defined basolateral sorting motifs. When we expressed FcRgammaII-B2 and CD44, two basolateral markers whose sorting depends on dihydrophobic motifs, they were unpolarized in hippocampal neurons. We also assessed the localization of the Epidermal Growth Factor Receptor (EGFR), a basolateral protein whose sorting signal contains a proline-rich motif and two dihydrophobic motifs. EGFR was restricted to the dendrites in neurons and relied on the same sorting signal for proper targeting. These results show that the dendritic sorting machinery in neurons does not recognize dihydrophobic-based basolateral sorting signals. In contrast, the sorting signal present in EGFR directs both basolateral and dendritic targeting and defines a novel dendritic targeting motif.