Neoplastic etiology was found in 33 of 450 patients with acute pericardial disease (7.3%). Acute pericardial disease was the first manifestation of previously unknown malignancies in 18 of 450 patients (4.0%), and lung cancer was the most common malignancy (72.2%, p = 0.02). The following clinical characteristics were associated with a greater probability of a neoplastic etiology: a history of malignancy (odds ratio [OR] 19.8), cardiac tamponade at presentation (OR 7.0), a lack of response to nonsteroidal anti-inflammatory drugs, and recurrent or incessant pericarditis (OR 10.0). A similar prognosis was found in patients with or without a history of known cancer.