Lipomatous hypertrophy of the interatrial septum (LHIS) is an increasingly recognized heart condition characterized by fatty deposits in the interatrial septum with sparing of the fossa ovalis. Its distinctive characteristic features by imaging techniques, benign nature, and the fact that most patients remain asymptomatic, has limited the need for histological confirmation and operative intervention in most cases. In this report, we describe two cases of LHIS where cardiac surgical intervention was indispensable: in the first patient, due to the presence of an additional left atrial tumour found out as mixoma and in the second, to relief a superior vena cava obstruction together with bypass grafts for severe coronary artery disease. Histological samples of the interatrial septal lesion were obtained in both cases either because of uncertainty of the diagnosis (Case 1) or to confirm the diagnosis (Case 2).