Seven muscle biopsies from patients with the clinical characteristics of Marinesco-Sjögren syndrome (MSS) revealed myopathic changes of two types; muscle fiber necrosis followed by regeneration and focal myofibrillar degeneration inducing autophagocytosis with rimmed vacuole formation. In two young patients, massive muscle fiber necrosis with phagocytic invasion was the predominant feature and autophagic phenomenon was minimal, resembling the findings in progressive muscular dystrophy. Myofibrillar degeneration with autophagic phenomenon was prominent in five adult patients. The coexistence of these two degenerative processes and the secondarily induced reactive changes of muscle fiber hypertrophy, interstitial fibrosis, occasional ragged-red fibers and type 1 fiber predominance, are responsible for the wide spectrum of muscle pathology in MSS. The dense double-membrane structure surrounding myonuclei, previously reported as being specific to MSS, was present in only one biopsy.