We report a new changing-look quasar, WISEJ105203.55+151929.5 at z=0.303, found by identifying highly mid-IR-variable quasars in the Wide-field Infrared Survey Explorer(WISE)/Near-Earth Object WISE Reactivation (NEOWISE) data stream. Compared to multiepoch mid-IR photometry of a large sample of SDSS-confirmed quasars, WISEJ1052+1519is an extreme photometric outlier, fading by more than a factor of two at 3.4 and 4.6 μm since 2009. Swift target-of-opportunity observations in 2017 show even stronger fading in the soft X-rays compared to the ROSAT detection of this source in 1995, with at least a factor of 15 decrease. We obtained secondepoch spectroscopy with the Palomar telescope in 2017 that, when compared with the 2006 archival SDSS spectrum, reveals that the broad Hβ emission has vanished and that the quasar has become significantly redder. The two most likely interpretations for this dramatic change are source fading or obscuration, where the latter is strongly disfavored by the mid-IR data. We discuss various physical scenarios that could cause such changes in the quasar luminosity over this timescale, and favor changes in the innermost regions of the accretion disk that occur on the thermal and heating/cooling front timescales. We discuss possible physical triggers that could cause these changes, and predict the multiwavelength signatures that could distinguish these physical scenarios.