Esophagitis dissecans superficialis (EDS), a rare desquamative esophageal disease of uncertain etiology, is characterized by sloughing of fragments of esophageal mucosa. To the best of our knowledge, there has been no reported case of EDS in an HIV-infected patient. We report the first case of EDS in an adult HIV-infected male, who was hospitalized due to dysphagia. Esophagogastroscopy was performed, and the endoscopic findings together with the histopathologic findings of esophageal tissues were consistent with EDS. However, his symptom of dysphagia was not explained by EDS, but was the early symptoms of muscle-specific kinase (MuSK) myasthenia gravis (MG) that we finally diagnosed later by progression of the symptoms and electrophysiologic study. His symptoms had gradually improved after a course of intravenous immunoglobulin treatment. This is the first case of EDS and MuSK myasthenia gravis in an HIV-infected patient. A high index of suspicion of EDS should be made when taking care of the patients with desquamative or sloughing esophagitis especially with unknown etiology.