We described the rare case of a 54-year-old male patient with an anomalous left main coronary artery, originating from the right sinus with a retro-aortic course. A significant distal left main coronary artery (LM) atherosclerotic lesion was identified and a successful PCI with direct stenting was performed. Coronary artery abnormalities represent the most technically challenging cases for interventional cardiologists. However, in selected cases, a percutaneous intervention can offer an effective and safe therapeutic option.

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