This paper presents a study on the impact of cirrus cloud heterogeneities on MODIS simulated thermal infrared (TIR) brightness temperatures (BT) at the top of the atmosphere (TOA) as a function of spatial resolution from 50 m to 10 km. A realistic 3-D cirrus field is generated by the 3DCLOUD model, and 3-D thermal infrared radiative transfer (RT) is simulated with the 3DMCPOL code. According to previous studies, differences between 3-D BT computed from a heterogeneous pixel and 1-D RT computed from a homogeneous pixel are considered dependent, at nadir, on two effects: (i) the optical thickness horizontal heterogeneity leading to the homogeneous plane parallel bias (PPHB) and the (ii) horizontal radiative transport (HRT) leading to the independent pixel approximation error (IPAE). A unique but realistic cirrus case is simulated and, as expected, the PPHB impacts mainly the low spatial resolution results (above 250 m) with averaged values up to 5–7 K while the IPAE impacts mainly the high spatial resolution results (below 250 m) with average values up to 1–2 K. A sensitivity study has been performed in order to extend these results to various cirrus optical thicknesses and heterogeneities by sampling the cirrus in several ranges of parameters. For four optical thickness classes and four optical heterogeneity classes, we have found that, for nadir observations, the spatial resolution where the combination of PPHB and HRT effects is the smallest, falls between 100 m and 250 m. These spatial resolutions appear thus to be the best choice to retrieve cirrus optical properties with the smallest cloud heterogeneity related total bias in the thermal infrared. For off-nadir observations, the average total effect is increased and the minimum is shifted to coarser spatial resolutions.