A novel approach to determine the thermodynamic solubility of tin in indium oxide via the exsolution from tin overdoped nano-ITO powders is presented. High-energy, in situ and ex situ synchrotron X-ray diffraction was utilized to study the solubility limit at temperatures ranging from 900°C to 1375°C. The tin exsolution from overdoped nanopowders and the formation of In4Sn3O12 were observed in situ during the first 4–48 h of high-temperature treatment. Samples annealed between 900°C and 1175°C were also studied ex situ with heat treatments for up to 2060 h. Structural results obtained from Rietveld analysis include compositional phase analysis, atomic positions, and lattice parameters. The tin solubility in In2O3 was determined using the phase analysis compositions from X-ray diffraction and the elemental compositions obtained from X-ray fluorescence. Experimental complications that can lead to incorrect tin solubility values in the literature are discussed.