In this work, we use electron diffraction to explore polytypism and the defect microstructure in xanthine crystals. Firstly, twinning about the [101] axes is observed in Form I. Secondly, we determine a new phase of xanthine (Form II). Using 3D-ED to elucidate its structure, we show that Form II is a polytype of Form I. Next, we apply 4D-STEM to highlight the spatial relationship and interfaces of twin boundaries and intergrowths between polytypes. Here, VDF imaging and distinct streaking in diffraction patterns indicate the presence of rigid-body translational planar disorder within domains. These insights are supported via a multi-phase Rietveld refinement (incorporating a stacking fault model) of in-situ high resolution synchrotron X-Ray powder diffraction (XRPD) data to demonstrate consistency between electron diffraction data and that from the XRPD of the bulk sample.