The normal physiological function of the prion protein PrP(C) remains elusive despite its widespread expression, particularly throughout the nervous system. A critical step toward identifying its function is to precisely localize its pattern of expression. Historically, the immunolocalization of PrP(C) has proved to be notoriously difficult and nonconsensual. We have thus undertaken a detailed expression analysis by means of a combination of in situ hybridization, knockout mice, and immunohistochemistry, using recently generated highly specific antibodies. We have attempted to accurately localize PrP(C) expression in a tissue that is highly structured and of crucial behavioral importance to mice, the olfactory system. We found that PrP(C) was expressed in both peripheral and central neurons of the olfactory system and that its distribution was axonal-specific in both olfactory sensory neurons of the olfactory epithelium and mitral cells of the olfactory bulb. Our detailed expression analysis and the axonal localization we observed may provide important hints toward potential functions of PrP(C).