Many regions of the Earth’s mantle are seismically anisotropic, including portions of the lowermost mantle, which may indicate deformation due to convective flow. The splitting of ScS phases, which reflect once off the core-mantle boundary (CMB), is commonly measured to identify lowermost mantle anisotropy, although some challenges exist. Here, we use global wavefield simulations to evaluate commonly used approaches to inferring a lowermost mantle contribution to ScS splitting. We show that due to effects of the CMB reflection, only the epicentral distance range between 60^◦ and 70^◦ is appropriate for ScS splitting measurements. For this distance range, splitting is diagnostic of deep mantle anisotropy if no upper mantle anisotropy is present; however, if ScS is also split due to upper mantle anisotropy, the reliable diagnosis of deep mantle anisotropy is challenging. Moreover, even in the case of a homogeneously anisotropic deep mantle region sampled from a single azimuth by multiple ScS waves with different source polarizations (in absence of upper mantle anisotropy), different apparent fast directions are produced. We suggest that ScS splitting should only be measured at “null” stations and conduct such an analysis worldwide. Our results indicate that seismic anisotropy is globally widespread in the deep mantle.