Introduction: Persistent left superior vena cava (PLSVC) is an abnormality of the thoracic vascular system resulting from the lack of regression of left cardinal vein to form the ligament of Marshall. The incidence in the general population is 0.3% but in 90% of the cases a bilateral upper vein is present and most commonly drains into the right atrium, through the coronary sinus. The association with the absence of the right superior vena cava is extremely rare, with important diagnostic and therapeutic implications. Although it is often asymptomatic and incidentally discovered, the presence of this anomaly hampers access to the right heart by cephalic or subclavicular approach, most commonly used technique for implantation of the cardiac devices. Methods: We present the case of a patient aged 59 years, in preoperative status for endometrial carcinoma, who was diagnosed with 2nd degree AV block. Echocardiography revealed normal left ventricular systolic function (EF 60%), but draws attention to a dilated coronary sinus of 24 mm. We decided that cardiac pacemaker is required and during the procedure the persistence of left superior vena cava is suspected. The procedure was difficult, and the placement of the active electrode in the right ventricle required use of the “hand- shaped” stiletto, due to the instability caused by unusual route of the electrode. The fixation of the atrial electrode failed and therefore we decided for a VVIR pacing. Results: Subsequently phlebography of the superior vena cava and CT angiography examination with contrast confirm the persistence of the left superior vena cava and the right superior vena cava agenesis. Th e evolution aft er procedure was favorable, with no local or systemic complications related with the stimulation procedure, and with the disappearance of clinical symptoms. Conclusions: Isolated persistent left superior vena cava is a rare anatomical variation (0.1%) of the thoracic venous system. The particularity of our case lies in its accidental discovery during cardiac pacemaker procedure. Close to 40% of patients with PVCSS associate other congenital cardiac disease, as well, like atrial septal defect or aortic coarctation, and 17% of them present architectural and anatomical abnormalities of the sinus node and atrioventricular conduction tissue. Cardiac pacing in patients with isolated persistent left superior vena cava remains a difficult procedure and there are described in the literature many cases of implant failed in these patients.