The impact of horizontal heterogeneities, liquid water path (LWP from AMSR-E), and cloud fraction (CF) on MODIS cloud effective radius (re), retrieved from the 2.1 μm (re2.1) and 3.8 μm (re3.8) channels, is investigated for warm clouds over the southeast Pacific. Values of re retrieved using the CERES algorithms are averaged at the CERES footprint resolution (∼20 km), while heterogeneities (Hσ) are calculated as the ratio between the standard deviation and mean 0.64 μm reflectance. The value of re2.1 strongly depends on CF, with magnitudes up to 5 μm larger than those for overcast scenes, whereas re3.8 remains insensitive to CF. For cloudy scenes, both re2.1 and re3.8 increase with Hσ for any given AMSR-E LWP, but re2.1 changes more than for re3.8. Additionally, re3.8–re2.1 differences are positive (<1 μm) for homogeneous scenes (Hσ < 0.2) and LWP > 45 gm−2, and negative (up to −4 μm) for larger Hσ. While re3.8–re2.1 differences in homogeneous scenes are qualitatively consistent with in situ microphysical observations over the region of study, negative differences – particularly evinced in mean regional maps – are more likely to reflect the dominant bias associated with cloud heterogeneities rather than information about the cloud vertical structure. The consequences for MODIS LWP are also discussed.