Acute coronary syndromes have heterogeneous clinical presentations, features and prognosis. They can also occur without angiographic evidence of significant coronary artery stenosis, based on multiple causes. We report on the diagnostic and therapeutic management of a 56-year-old man with an acute coronary syndrome and angiographic evidence of non-obstructive coronary artery disease. In addition to the basic angiographic evaluation, intracoronary imaging was here helpful to understand the underlying mechanism, prompting a tailored therapeutic strategy and avoiding inappropriate treatment with percutaneous coronary intervention and stenting. This clinical case here described offers the opportunity to briefly recapitulate the most meaningful milestones in the progress in the pathophysiology of acute coronary syndromes, also focusing on myocardial infarction non-obstructive coronary artery, and to appreciate the occurrence of rare cases and consequent lessons.