Objective To investigate the clinicopathological features of chronic progressive external ophthalmoplegia (CPEO).Methods A retrospective analysis was performed for the clinical data of five patients who were diagnosed with CPEO in our hospital from October 2015 to July 2017 to investigate the clinical features and pathological features of the skeletal muscle.Results There were two male and three female patients, which were all sporadic cases, with a mean age of onset of 27.8±12.56 years (range 15-51 years). Four patients had an initial symptom of blepharoptosis and one had an initial symptom of diplopia. All of the five patients had blepharoptosis and ocular motility disorders, among whom two had diplopia, one had mild weakness of the cervical flexor and the proximal limb muscles, and one had menarche at the age of 19 years with short stature. All five patients had negative results of neostigmine test and serum acetylcholine receptor antibody test. Only one patient had a mildly elevated level of creatine kinase (251 U/L). One patient had complete right bundle branch block based on electrocardiographic findings. Electromyography was performed for all five patients, among whom two had myogenic changes in some of the muscles examined. All patients had normal repeated electrical nerve stimulation and head MRI findings. Major pathological changes of the skeletal muscle included abnormal increases in ragged red fibers (RRF), ragged blue fibers, and cytochrome C oxidase (COX)-negative muscle fibers.Conclusions Major clinical features of patients with CPEO include progressive blepharoptosis and ocular motility disorders, and some patients may have diplopia, mild weakness of the proximal limb muscles, heart block, and growth retardation. Skeletal muscular pathology is the main diagnostic measure and shows abnormal increases in RRF and COX-negative muscle fibers.