Among unselected patients presenting with acute chest pain the prevalence of ACS may be summarized as following: 5-10% STEMI, 15-20% NSTEMI, 10% unstable angina and 15% other cardiac conditions. Hence there is about 50% of chest pain cases with a diagnosis of non-cardiac disease warranting the need for an adequate differential diagnosis.The main conditions that should be considered are the life-threatening ones such as aortic dissection, pulmonary embolism or tension pneumothorax. Other conditions often misdiagnosed are myopericarditis, cardiomyopathies, acute heart failure, tachyarrhythmias or aortic valve stenosis: an echocardiography is thereby recommended in any case of hemodynamic instability to confirm the cardiac origin (15). Moreover, even a chest X-ray should be performed in case of unlike ACS to detect pneumonia, pneumothorax, rib fractures or other thoracic disorders. Finally, musculoskeletal pain as well as esophagitis/reflux should be always taken into account since these are very common causes of chest disorders.