Clinically amyopathic dermatomyositis (CADM) is associated with antibodies directed against the protein encoded by the melanoma differentiation-associated gene 5 (MDA5). CADM patients have an increased risk of developing rapidly progressive interstitial lung disease (RP-ILD) and spontaneous pneumomediastinum. Two Peruvian cases of RP-ILD-associated CADM with spontaneous pneumomediastinum are presented, one of them was anti-MDA5 antibody positive. To our knowledge, this is the first report of anti-MDA5-associated CADM in the Peruvian population.