Characterizing the lateral organization of lipid membranes is important for understanding the function of cell membranes. The most common way to determine miscibility phase behavior is using fluorescence microscopy, where the presence of separate phases is imaged by the preferential partitioning of a labeled lipid. However, fluorescence microscopy requires adding an additional lipid component, and can also lead to photooxidation. Interference scattering microscopy (iSCAT) is a label-free imaging technique that images the differences in light scattering from different regions of a sample. iSCAT is capable of imaging coexisting domains. We quantify the sensitivity of iSCAT to physical parameters including thickness mismatch, topography, and the presence of defects.