Tyrosine kinase inhibitors (TKI) or monoclonal antibodies targeting EGFR, HER2 or VEGFR receptors have demonstrated substantial clinical benefit in patients with advanced breast cancer, colon cancer, head and neck cancer, non-small cell lung cancer, and renal cell carcinoma. Nevertheless, these drugs have some target related adverse effects, particularly cardiovascular toxicities. We report here the case of a patient included in a phase I trial of a new compound, a tyrosine kinase inhibitor targeting HER1, HER2, HER4 and VEGFR2. The patient developed during this treatment an acute and transient left ventricular systolic dysfunction. Careful management of this adverse effect allowed the patient to continue therapy and to achieve a major partial response.