AbstractObjectivesDescribe the histopathology of the temporal bones in MELAS (myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes) syndrome. The syndrome results from a known point mutation in mitochondrial DNA.MethodsHistopathology analysis of a pair of temporal bones from the oldest surviving MELAS syndrome temporal bone donor. Histopathologic findings were correlated with known premortem clinical data.ResultsThe inner ears showed severe but incomplete atrophy of the stria vascularis for the length of the cochleae. In contrast, the organ of Corti and inner hair cells appeared intact with some loss of outer hair cells. Other than moderate loss at the basal turn, spiral ganglion cells numbers were normal. The vestibular neuroepithelium was mostly normal with the exception of moderate degeneration of the macula sacculi and partial collapse of the saccular wall on the right. The cerebral cortex had infarct‐like lesions with adjacent gliosis.ConclusionThis is an analysis of the oldest patient with MELAS syndrome to date, an addition to only two previously published patients. It supports the notion that hearing loss is a result of dysfunction of the stria vascularis and not loss of hair cells or neurons. Patterns of vestibular pathology are in agreement to in‐vivo measurements. These findings support auditory rehabilitation with cochlear implants and may be relevant to hearing loss due to other mitochondrial mutations.Level of evidence4