A 38 years old woman without any cardiovascular risk was admitted to the Emergency Room of our Hospital symptomatic for chest pain and dyspnoea. She referred a recent holiday in Tunisia; she was excellent health until a week before when she developed flue-like symptoms, such as fever, fatigue, abdominal pain, diarrhea and myalgia, like all the family members; the night before the access to the ER, she suffered from weakness of breath. Physical examination revealed venous engorgement and sinus tachycardia with a rate of 102 bpm, blood pressure was about 85/50 mmHg, oxygen saturation in 3L nasal cannula was 92%. The EKG showed a sinus tachycardia without any ST elevation or depression and generalized low voltage. A transthoracic echocardiography revealed circumferential pericardial effusion (3,5 cm) and both right atrium and right ventricle collapse in the setting of cardiac tamponade; EF was 35% (GLS=6%). Our first clinical suspicion was viral pericarditis with pericardial effusion (early cardiac tamponade), in consideration of the anamnestic data, the holiday in Tunisia and the general symptoms. However, an urgent pericardiocentesis was performed and one liter of sero-sanguineous pericardial fluid (exudate) was drained; therefore, there was an immediate haemodynamic improvement. A pigtail was placed using the Seldinger technique. While the first sample of cytology on sero-sanguineus pericardial fluid was negative, the second sample resulted positive for malignancy. Chest CT showed bilateral pleural effusion and a mass which was compatible with a lung cancer. Lung nodule biopsy revealed a lung adenocarcinoma. Immunohistochemistry (IHC) and molecular testing for epidermal growth factor receptor (EGFR) were positive. The patient was affected by metastatic non small cell lung cancer with EGFR mutation, which was responsive to Osimertinib. Three days later, another echo was performed showing almost complete resolution of pericardial effusion and normal LV function (EF= 55%). The patient was transferred to the Oncology Department and then discharged from the Hospital. Before starting Osimertinib, she was suggested to undergo a baseline cardiovascular stratification, EKG and transthoracic echocardiogram, three-monthly echocardiography surveillance with monitoring of GLS (which guides the management of potentially cardiotoxic drugs); close monitoring of magnesium levels is also recommended to minimize the risk of QTc prolongation.