Background <p>The majority of coronary artery anomalies are harmless and asymptomatic. However, in rare cases, they have been linked to myocardial ischemia and sudden cardiac death. One of the most frequently occurring coronary anomalies is the aberrant origin of the circumflex coronary artery (Cx) from the right coronary sinus.</p> Case presentation <p>We present a case of a 59-year-old man who suffered an inferior ST-segment elevation myocardial infarction. His coronary angiography revealed severe multivessel coronary artery disease (CAD) and anomalous origin of the Cx. The case presented a diagnostic challenge regarding whether the right coronary artery (RCA) or the anomalous Cx was the primary culprit. This uncertainty was further compounded by the fact that established algorithms for differentiating the culprit artery may not be directly applicable to anomalous coronary arteries. Primary percutaneous coronary angiography (PCI) was performed on the RCA. PCI to the anomalous Cx was challenging due to difficulty in coronary engagement and wiring. This was complicated by extensive dissection, which was managed through re-wiring and the placement of multiple stents. The left anterior descending artery stenting was uneventful. The patient had a favorable final angiographic and clinical outcome and has been asymptomatic for one year.</p> Conclusions <p>This case demonstrates the successful diagnosis and management of ACS in the context of multi-vessel CAD and an anomalous circumflex coronary artery. It highlights significant diagnostic challenges stemming from the lack of specific algorithms for such cases and the considerable management complexities faced during PCI. These insights underscore the critical need for tailored approaches and updated guidelines to effectively address similar intricate scenarios.</p>