In vertebrate olfactory transduction a calcium-dependent chloride efflux greatly amplifies the odorant response. Indeed, the binding of odorants to receptors in the cilia of olfactory sensory neurons activates a transduction cascade that involves the opening of cyclic nucleotide-gated channels and the entry of calcium in the cilia. Calcium activates a chloride current that, in the presence of a maintained elevated intracellular chloride concentration, produces an efflux of chloride ions and amplifies the depolarization. Despite the relevant physiological role played by calcium-activated chloride channels in olfactory transduction, as well as in several other physiological processes, their molecular identity is still unclear. We showed by immunohistochemistry that anoctamin2/TMEM16b is expressed in the ciliary layer of mouse olfactory sensory neurons and performed an extensive functional comparison using both inside-out and whole-cell voltage-clamp techniques to record currents in the ciliary region of mouse isolated olfactory sensory neurons and in HEK293 cells transfected with anoctamin2/TMEM16b. Our findings support the hypothesis that anoctamin2/TMEM16b is a promising candidate to be part of the native olfactory channel, which contributes to the chloride-based amplification in olfactory transduction.