This article provides an up-to-date overview of pericardial effusion in oncological patients and offers guidance on its management. It addresses the question of when malignancy should be suspected in cases of newly diagnosed pericardial effusion. Cancer-related pericardial effusion is often the result of lung, breast, melanoma, or lymphoma metastasizing to the pericardium via direct invasion, lymphatic dissemination, or hematogenous spread. Several cancer therapies can also cause pericardial effusion, typically during or shortly after administration. Pericardial effusion following radiation therapy may develop years after treatment. Other causes include infections and primary tumors of the pericardium. The diagnosis of cancer-related pericardial effusion is usually incidental, but it accounts for about one-third of all cardiac tamponades. Drainage, primarily through pericardiocentesis, is necessary when cancer or cancer treatment-related pericardial effusion impairs hemodynamics. A pericardial catheter is recommended for 2-5 days after pericardiocentesis. Large pericardial effusions should be managed conservatively if the patient is stable, although the optimal monitoring frequency and timing by echocardiography are yet to be established. Pericardial effusion secondary to immune checkpoint inhibitors often responds to corticosteroid therapy. In cases of newly found pericardial effusion in individuals without active cancer or recent cancer treatment, a history of malignancy, unremitting or recurrent course, large effusion, presentation with cardiac tamponade, incomplete response to empirical therapy with nonsteroidal anti-inflammatory drugs, and hemorrhagic fluid at pericardiocentesis suggest a neoplastic etiology.This article provides an up-to-date overview of pericardial effusion in oncological patients and offers guidance on its management. It addresses the question of when malignancy should be suspected in cases of newly diagnosed pericardial effusion. Cancer-related pericardial effusion is often the result of lung, breast, melanoma, or lymphoma metastasizing to the pericardium via direct invasion, lymphatic dissemination, or hematogenous spread. Several cancer therapies can also cause pericardial effusion, typically during or shortly after administration. Pericardial effusion following radiation therapy may develop years after treatment. Other causes include infections and primary tumors of the pericardium. The diagnosis of cancer-related pericardial effusion is usually incidental, but it accounts for about one-third of all cardiac tamponades. Drainage, primarily through pericardiocentesis, is necessary when cancer or cancer treatment-related pericardial effusion impairs hemodynamics. A pericardial catheter is recommended for 2-5 days after pericardiocentesis. Large pericardial effusions should be managed conservatively if the patient is stable, although the optimal monitoring frequency and timing by echocardiography are yet to be established. Pericardial effusion secondary to immune checkpoint inhibitors often responds to corticosteroid therapy. In cases of newly found pericardial effusion in individuals without active cancer or recent cancer treatment, a history of malignancy, unremitting or recurrent course, large effusion, presentation with cardiac tamponade, incomplete response to empirical therapy with nonsteroidal anti-inflammatory drugs, and hemorrhagic fluid at pericardiocentesis suggest a neoplastic etiology.