Although histologically benign, cardiac papillary fibroelastoma (CPF) has a high propensity for systemic embolization. We report details of four patients with different clinical histories who underwent surgical excision of diagnosed valvular CPF. Correlations between clinical data, histological and immunohistochemical studies were demonstrated through the importance of anatomic and functional integrity of the endothelial superficial layer to prevent the risk of thrombus formation. Although blood turbulence may influence the genesis of these tumors, the presence of dendritic cells being involved in the immunity process provided direct evidence of remnant traces of cytomegalovirus, and suggested the existence of a virus-induced tumoral mechanism.