ABSTRACT We present the first detection of the photometric variability in a spectroscopically confirmed Y dwarf. The Infrared Array Camera on board the Spitzer Space Telescope was used to obtain time series photometry of WISE J140518.39+553421.3 at 3.6 and 4.5 m over a 24-hr period at two different epochs separated by 149 days. Variability is evident at 4.5 m in the first epoch and at 3.6 and 4.5 m in the second epoch, which suggests that the underlying cause or causes of this variability change on the timescales of months. The second-epoch 3.6 and 4.5 light curves are nearly sinusoidal in form, in phase, have periods of roughly 8.5 hr, and have semi-amplitudes of 3.5%. We find that a simple geometric spot model with a single bright spot reproduces these observations well. We also compare our measured semi-amplitudes of the second-epoch light curves to predictions of the static, one-dimensional, partly cloudy, and hot spot models of Morley and collaborators, and find that neither set of models can reproduce the observed 3.6 and 4.5 semi-amplitudes simultaneously. Therefore, more advanced two-dimensional or three-dimensional models that include time-dependent phenomena like vertical mixing, cloud formation, and thermal relaxation are sorely needed in order to properly interpret our observations.