The term cardiomyopathy is used to describe heart disease resulting from an abnormality in the myocardium. It is rare in cynomolgus macaques (Macaca fascicularis). Here, we report a case of hypertrophic cardiomyopathy in an 11-year-old male cynomolgus macaque. Macroscopically, the interventricular septum (IVS) and the left ventricular (LV) and right ventricular (RV) walls of the heart were thickened. Histologically, cardiomyocytes showed hypertrophy and disarray with interstitial fibrosis, and some myocytes showed karyomegaly and vacuoles. On the basis of these morphological characteristics, the present case was diagnosed as hypertrophic cardiomyopathy. Immunohistochemically, the cardiomyocytes in the affected regions were positive for the autophagic markers LC3 and p62/SQSTM1 (p62). The accumulation of autophagosomes in hypertrophied cardiomyocytes was demonstrated. The mechanism of accumulation of autophagosomes seems to be a secondary effect due to stress. To our knowledge, this is the first report of spontaneous hypertrophic cardiomyopathy in a cynomolgus macaque.