A combination of spatially collocated Atmospheric Infrared Sounder (AIRS) radiances and Moderate Resolution Imaging Spectroradiometer (MODIS) cloud products are used to quantify the impact of cloud heterogeneity on AIRS-based assessments of cloud thermodynamic phase. While radiative transfer simulations have demonstrated that selected AIRS channels have greater sensitivity to cloud thermodynamic phase in comparison to the relevant MODIS bands, the relative trade-offs of spectral and spatial resolution differences that are inherent between AIRS and MODIS have not been quantified. Global distributions of AIRS field-of-view scale frequencies of clear sky (13–14%), heterogeneous cloud (26–28%), and homogeneous cloud (59–60%) are quantified for a four week time period using cloud fraction, and further categorization of cloud uniformity is assessed with the variance of cloud top temperature. Homogeneous clouds with window brightness temperatures (Tb) between 250 and 265 K are shown to have larger cloud thermodynamic phase signatures than heterogeneous clouds. Clouds in this limited Tb range occur 30–50% of the time in the mid- and high latitude storm track regions, are generally difficult to identify as being water or ice phase, and show strong responses in forced CO2 climate change modeling experiments. Two-dimensional histograms of Tb differences sensitive to cloud phase (1231–960 cm−1) and column water vapor (1231–1227 cm−1) show distinct differences between many homogeneous and heterogeneous cloud scenes. The results suggest the potential for a quantitative approach using a combination of hyperspectral sounders with high-spatial-resolution imagers, and their derived geophysical products, to assess cloud thermodynamic phase estimates within increasingly complex subpixel-scale cloud variability.