We report the case of a young woman with CMV infection, high level of creatine kinase and myopathy. Electromyography showed a myopathic pattern. Muscle biopsy showed a marked increase of NADH enzymatic activity in the central area of almost all type I fibres, few degenerative and necrotic fibres and scattered mononuclear cell infiltrates. Ultrastructural analysis showed a marked disarrangement of sarcomeric structure and large inclusions of thin filaments in some fibres, while immunohistochemistry evidenced alteration in desmin, actin and αB-crystallin protein signals. PCR for CMV detection on muscle sections was negative. Histological, immunological and ultrastructural evaluations were compatible with a necrotic inflammatory myopathy. The correlations between CMV liver infection and the myopathic pattern are discussed. This case underscores the need to consider CMV infection in the differential diagnosis of myopathy with undetermined aetiology, quickly providing directions for a targeted muscle pharmacological intervention.