The mammalian olfactory system has evolved the capacity to detect and discriminate between millions of odorants and to trigger appropriate behavioral actions in response to these sensory stimuli. While much has been learned about how olfactory sensory neurons detect odorants and signal their presence, the mechanisms by which specific innate, unlearned behaviors are initiated in response to ethologically relevant odors remains incompletely understood. Here, we present evidence revealing that CD20 functions as a mammalian odorant receptor that recognizes compounds produced by the natural mouse predators, the wolf and the ferret. CD20 is expressed in a previously uncharacterized subpopulation of olfactory sensory neuron in the main olfactory epithelium of the murine nasal cavity, and genetic deletion of CD20 results in mice which are unable to appropriately avoid predator derived odorants. Together, this work reveals a novel mechanism by which odors that trigger innate behaviors critical for organismal survival are sensed by the mammalian olfactory system.