Introduction: We are presenting the case of a 76 year old patient with medical history of deep venous thrombosis localized in the right inferior limb, associating non-Hodgkin malignant lymphoma with small cells grade 3B who was admitted for pleuritic thoracic pain, dyspnea at rest and intense fatigability. Methods: The physical exam revealed a tachypneic patient, with an increased heart rate, low blood pressure (90/60 mm Hg), Sp O2 86%, 3/6 systolic murmur in the tricuspid area, cold extremities. An acute pulmonary embolism was suspected due to an 11 points Geneva score and a 7 points Wells score, as well as increased plasma D-dimer levels; thus, an emergency transthoracic echocardiogram was performed, showing dilated right heart cavities, interventricular septal shift , McConnel sign, pulmonary hypertension, grade 3 tricuspid regurgitation. The CT pulmonary angiogram confirmed the presence of massive pulmonary embolism, localized bilaterally with aspect of saddle embolus. Results: Therefore, we started systemic thrombolysis with Streptokinase during 72 hours. At the end of the thrombolytic therapy, the patient underwent a control CT pulmonary angiogram that showed the absence of pulmonary arteries thrombosis. The echocardiography revealed the remission of the right cavities strain and the clinical and paraclinical evolution of the patient was favorable. Conclusions: The thrombolytic therapy in patients with fragile fibrinolytic balance, such as those with associated neoplasia, may cause fatal hemorrhagic complications. Therefore, thrombolysis is indicated only in massive pulmonary embolism with an increased mortality risk. This case supports the use of systemic thrombolysis for the treatment of fragile patients such as the ones associating ongoing malignancies.