Necrosis and regeneration of scattered muscle fibers are common features of many active acquired and immune myopathies. We studied a series of patients with acquired myopathies with an unusual pattern of regional, rather than scattered, muscle fiber necrosis and regeneration. Retrospective review of records of 7 patients with acquired myopathies having regional muscle fiber necrosis on muscle biopsy. Clinical features of patients included proximal symmetric weakness in arms and legs with a subacute onset (100%) beginning at ages between 41 and 92 years, with dysphagia (83%), myalgias (100%), skin rash (67%), and associated malignancy (71%). Serum creatine kinase was often very high (>1,600 U/L) (83%). Survival was less than 1 year in 43%. Myopathology included a regional distribution with muscle fiber necrosis and capillary loss in the border zones between intermediate-sized perimysial vessels, vascular pathology with damaged walls of intermediate-sized perimysial veins, and connective tissue with expression of the ischemia marker carbonic anhydrase IX but no mononuclear cell inflammatory foci. These data indicate that regional ischemic immune myopathies are likely caused by ischemia in border zones between damaged intermediate-sized perimysial blood vessels. Regional ischemic immune myopathies are a distinctive pathologic group of acquired, probably immune, noninflammatory dermatomyopathies with weakness and often a skin rash and systemic neoplasm.