In this histopathological comparison of 12 adult and 5 pediatric patients with HOCM, we demonstrated that Smad2/3 protein expression was significantly increased in the ventricular septal tissue in HOCM patients with extensive myocardial fibrosis, which indicated that the Smad2/3 signaling cascade is a persistent stimulus for the development of hypertrophic cardiomyopathy. The gene discussed is SMAD2; the disease is hypertrophic cardiomyopathy.