BACKGROUND: Pericardial mesothelioma cyst occurs rarely, and is often found incidentally. The coexistence between large pericardial mesothelial cyst and hypertrophic obstructive cardiomyopathy (HOCM) can make difficulties in medical management.CASE REPORT: Our case was a 33-year-old man presented with dizziness and pallor while standing since four years before, and recent syncope. On admission, transthoracic echocardiography reveled presence of hypertrophic cardiomyopathy in association with relatively small right ventricular and atrium due to compression effect by a large echo-free space at the right side of heart suggestive of pericardial cyst. Cardiac computed tomography confirmed presence of HOCM and large pericardial cyst. Patient underwent surgical septal myectomy and large mesothelial pericardial cyst excision because of persistent symptoms and compression effect of cyst on the right chambers despite beta-blocker therapy.CONCLUSION: To best of our knowledge, the coexistence of the large pericardial mesothelial cyst and HOCM has not been reported before.