Secondary ion mass spectrometry using the argon cluster primary ion beam enables molecular compositional depth profiling of organic thin films with minimal loss of chemical information or changes in sputter rate. However, for depth profiles of thicker organic films (> 10 μm of sputtered depth) we have observed the rapid formation of micron-scale topography in the shape of pillars that significantly affect both the linearity of the sputter yield and depth resolution. To minimize distortions in the 3D reconstruction of the sample due to this topography, a step-wise, staggered sample rotation was employed. By using polymer spheres embedded in an organic film, it was possible to measure the depth resolution at the film-sphere interface as a function of sputtered depth and observe when possible distortions in the 3D image occurred. In this way, it was possible to quantitatively measure the effect of micron-scale topography and sample rotation on the quality of the depth profile.