Serum biomarkers detect the earliest events in disease, monitor management, and provide insight into disease pathogenesis. At this time, there are no biomarkers available for otologic disorders. Otolin-1 is a scaffolding protein exclusively expressed in otoconia and cells of the vestibule and the cochlea; therefore, it may be a biomarker candidate for assessing the health of the inner ear. As a proof of concept, we used serum samples from controls without otologic history and subjects with a history of benign paroxysmal positional vertigo (BPPV), performed enzyme-linked immunosorbent assay for otolin-1, and measured the optical density of the substrate. Otolin-1 was detectable and quantifiable in all subjects, indicating that this inner ear protein crosses the blood-labyrinthine barrier. Furthermore, subjects with BPPV had significantly higher levels, with about one-third being above the control range. This promising preliminary result suggests that inner ear-specific proteins have the potential to serve as biomarkers for otologic disease processes.