Chest pain is one of the most frequent symptoms of cardiac disease, but it can be also provoked by other reasons. It is not easy to establish the cause of chest pain, nevertheless it plays a key role in the diagnostic workup. In the differential diagnosis first of all it is necessary to take into account the most common diseases and those which may be fatal or detrimental for the patient’s health. The most important are myocardial ischaemia and myocardial infarction. During the clinical assessment it is necessary to consider the possible reason of the chest pain originated deep from the chest (aorta, pulmonary artery, mediastinum, oesophagus, trachea, bronchi, pleura), from the chest wall (sensor nerves, chondrocostal junctions, spine, skin), from the abdomen (stomach, duodenum, pancreas, gall bladder) and also symptoms of psychological origin. In the diagnostic process it is necessary to take into account the chest pain characteristics, duration of chest pain, triggering and relieving factors and also coexisting symptoms. A subject with chest pain should be treated as a patient of high cardiovascular risk until the diagnostic management is terminated. The precise differential diagnostics allows to establish the correct diagnosis and to initiate the appropriate treatment. This paper describes five patients with a chest pain. Despite similar symptoms every patient has different disease and the clinical outcome was completely different in every case.