Introduction: Superior vena cava syndrome is described as the obstruction of blood flow through the superior vena cava. The literature reports that the incidence of this pathology varies from 1 case in every 650 inhabitants and 1 case in every 3 100 inhabitants. Since this condition is very rare in the pediatric population, no clear figure has been reported regarding its incidence in children. The use of a central venous catheter in newborns is a risk factor for this condition, as it may cause a thrombus due to the inflammatory reaction against the device. Therefore, it is necessary to initiate anticoagulation management and remove the catheter.Case presentation: Premature male newborn, (31.4 weeks gestation), with acute respiratory distress syndrome, early neonatal sepsis, pneumonia, necrotizing enterocolitis on 2 occasions, intestinal obstruction due to adhesions and intestinal volvulus. At 90 days of age, he presented thrombosis of the superior vena cava without involvement of the jugular and subclavian vein junction in the right atrium. Anticoagulant management was started, but given his unfavorable evolution, a multidisciplinary medical board was held to assess the risks, benefits, and treatment options in this age group. It was decided to start intracavitary tissue plasminogen activator treatment associated with mechanical thrombectomy and angioplasty of the superior vena cava. Due to the difficulty of conducting clinical trials in this population and the rates of major bleeding complications obtained with thrombolytic therapies, there is very little information available on the use of tissue plasminogen activator in newborns. For this reason, alteplase is seldom considered as the therapy of choice. However, in patients with life-threatening thrombosis, such as the present case, the results obtained in adults could be extrapolated in search of a favorable outcome.Conclusions: Fibrinolytic therapy is a way to reduce the size of the thrombus, but it dramatically increases the risk of bleeding; consequently, these patients must be strictly monitored. In pediatric populations, due to the diameter of the blood vessels, thrombectomy is difficult to perform; additionally, recurrent thrombosis and the need for transfusion of blood products are frequent.