In this work, we use operando Scanning Xray Diffraction Microscopy (SXDM) to reveal the relationship between microstructural defects, strain, and phase transitions inside LiNi 0.5 Mn 1.5 O 4 (LMNO) spinel single crystals. This relatively new technique combines sub 100 nm spatial resolution with the extreme sensitivity to strain and crystallographic orientation of X-ray diffraction. To compensate for the statistical limitations of SXDM (i.e. a limited number of simultaneously measured particles due to a restricted imaging area and relatively low imaging speed) we used operando Multicrystal X-ray Diffraction (MCXD) by alternating between those two modes of measurements. MCXD (also sometimes referred to as single-particle X-ray diffraction (SP-XRD) ) is similar to conventional powder diffraction but examines individual Bragg reflections with a ∼ 100 µm X-ray beam and thus allows to study the d-spacing and lattice plane misorientation for ensembles of multiple single crystal particles. This technique provides useful information that bridges the gap between singleparticle (BCDI, SXDM) and macroscopic techniques (powder XRD). For example in Ref. , plane reorientation was found to be a distinctive characteristic of the phase transformation in sodium-ion NNMO cathode material. LMNO exhibits two phase transitions, proceeding from a fully lithiated state (LiNi 0.5 MnO 4 , mentioned as Li 1 hereafter) to a half lithiated intermediate (Li 0.5 Ni 0.5 Mn 1.5 O 4 , Li 0.5 ) and then to complete delithiation (Ni 0.5 Mn 1.5 O 4 , Li 0 ). The reaction boundary is imaged across a single microcrystal during each phase transition. SXDM demonstrates that nanodomains of the newly appearing phases are not aligned with the lattice of the original particle. Instead, (de)lithiation creates new crystallites separated by small angle grain boundaries. They slowly merge and reconstruct the parent crystal once the phase transition is complete. These self-healing mosaic domains appear to be templated by persistent defects located inside the single crystals.