Massive pericardial effusion (PE) is a rare clinical encounter in children that usually develops insidiously with no specific clinical signs or symptoms. Unless recognized and managed early, affected patients may develop sudden hemodynamic deterioration with circulatory collapse due to cardiac tamponade, responsible for significant morbidity and mortality. In adults, massive PE is frequently seen in an advanced stage of intrathoracic malignancies, especially lung, breast, and esophageal cancer, called malignant PE. Occurrence of malignant PE in adults is considered an advanced stage of malignancy indicating poor prognosis. Massive PE can occur in children with cancer but less frequently and with quite a different clinical background compared to adults. However, emerging incidence of massive PE has been reported in conjunction with the recent trend of implementing more aggressive and newer cancer treatment strategies that substantially modulate a host immune system. With evolving cancer treatment, it is expected the incidence of massive PE may increase even in pediatric oncology patients. However, underlying mechanisms of massive PE in childhood malignancy are poorly understood. In this entry, we will review the pathogenesis of massive PE in malignancy in general and aim to characterize the contributing factors and clinical presentation of massive PE in pediatric oncology patients.