Background and Purpose— Most diffusion MRI studies of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode stroke-like lesions report high- or normal-apparent diffusion coefficient, and this has been used to differentiate stroke-like lesion from ischemic stroke. There are, however, 3 recent reports of restricted diffusion in the acute phase of the stroke-like lesions. The purpose of our study was to investigate this apparent paradox. Methods— We performed 9 serial MRI covering 2 stroke-like episodes in a 36-year-old man with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode caused by the common mitochondrial DNA mutation 3243A>G . Results— We found clear evidence of initial restricted diffusion in the stroke-like lesions, which gradually evolved to high-apparent diffusion coefficient as lesions aged. Evolution was, however, asynchronous with both high- and low-apparent diffusion coefficients temporally coexisting. Conclusions— Our findings suggest that cytotoxic edema does occur early in the course of a stroke-like lesions and that its presence or, conversely, the absence of vasogenic edema, should not weaken the possibility of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode in favor of ischemic stroke.