BACKGROUND Primary pericardial mesothelioma (PPM) is a rare malignancy with a high prevalence of mortality. The diagnosis is usually challenging using a variety of imaging modalities and invasive procedures and is generally performed at the later stages of the disease or in autopsy. This case study points to an unconventional presentation of PPM and the challenges in diagnosing this rare mortal malignancy. METHODS This study presents a 44-year-old woman with no remarkable medical history with an initial diagnosis of effusive constrictive pericarditis at first hospitalization. Imaging evaluations, including transthoracic echocardiography and chest computed tomography scan, demonstrated visible thickened pericardium, pericardial effusion, and mass-like lesions in pericardium and mediastinum. The definite diagnosis of primary pericardial mesothelioma was established after pericardiectomy and histopathology examinations. Chemotherapy with pemetrexed and carboplatin was administrated to the patient, and she has been through four cycles of chemotherapy with no complications to date. CONCLUSIONS Constrictive pericarditis is an uncommon presentation of PPM. Due to the high mortality rate and late presentation, difficulties and uncertainties in diagnosis, being aware of this rare malignant entity in different cardiac manifestations, particularly when there is no clear explanation or response to treatment in such conditions, is highly important.