<p>Brugada syndrome (BrS), a genetic disease with complex pathophysiology due to genetic and pharmacological factors, might lead to ventricular arrythmia and sudden cardiac arrest. Entrectinibe, a novel kinase inhibitor, is currently used for the treatment of metastatic of non-small cell lung cancer (NSCLC). Its adverse effects include rarely cardiotoxicity, malignant arrythmias and left ventricular myocardial dysfunction, which is highlighted in this case report. We present the case of a 52-year-old Caucasian female with a history of NSCLC and a recent initiation of Entrectinib due to cancer relapse. Three days later, the patient was diagnosed with almost asymptomatic atrial fibrillation (AF) and left bundle branch block (LBBB) which were automatically converted to sinus rhythm and a Brugada Type I pattern, which in turn was automatically resolved and replaced by a normal ECG pattern. The above-described ECG phenomena lasted for just a few hours. Entrectinib treatment was discontinued after Oncology consultation. Unexpected cardiotoxicity and arrhythmogenicity should be monitored when administrating new anti-cancer drugs. In the case of pre-existing Brugada pattern, Entrectinib is contra-indicated as it can followed by malignant ventricular arrhythmias. Additionally, treatment with Entrectinib must be interrupted in the presence of a QT prolongation (&gt; 500msec) or/and syncope or when a newly diagnosed Brugada pattern appears. The management of these patients must be individualized according to their status and the existence of comorbidities while the role of a Cardiologist is essential.</p>