We report two cases presented with a clinical picture of acute myocardial ischemia, chest pain and giant negative T waves on electrocardiogram (absent in previous tracings). The echocardiogram B-Mode showed in both cases an asymmetric left ventricular hypertrophy caused, respectively, by hypertrophic cardiomyopathy and hypertensive heart disease. Short-term electrocardiographic evolution to complete normalization was observed in both cases. The echo-dipyridamole test did not show dissynergias and this fact suggested the absence of coronary artery disease; this hypothesis was confirmed by a normal coronary angiography. We suppose that in both patients a few factors contributed to the ischemic events: respectively an acute anemia due to gastric bleeding and high blood pressure values. This clinical presentation is an example of a difficult differential diagnostic problem between left ventricular hypertrophy and acute myocardial ischemia, as it shows that giant negative T waves in hypertrophic cardiomyopathy do not necessarily depend on left myocardial hypertrophy involving the apex or other segments but may be associated to an acute myocardial ischemia related or not to a coronary artery disease. A correct evaluation of these clinical cases is important for clinical, therapeutic and prognostic implications.