Background: Guillain-Barré syndrome (GBS) is an acute immune-mediated disorder in the peripheral nervous system (PNS) characterized by symmetrical limb weakness, sensory disturbances, and clinically absent or decreased reflexes. Pantalgia and dysautonomia, including cardiovascular abnormalities, are common findings in the spectrum of GBS. It is usually challenging to distinguish GBS-related electrocardiogram (ECG) abnormities and chest pain from acute coronary syndrome (ACS) in patients with GBS due to the similar clinical symptom and ECG characteristics. Here, we present a case of GBS complicating ACS. Case Summary: A 37-year-old woman with a 2-month history of GBS presented to the emergency department due to pantalgia. The ECG showed a pattern of transitional T-wave inversion in the leads I, aVL, and V2 through V4 and shortly returned to normal, which appeared several times in a short time, but lab testing was unremarkable. Then, a further coronary computed tomography angiography (CTA) revealed the presence of critical stenosis of the left anterior descending artery, leading to the diagnosis of ACS. During the follow-up, she suffered from a non-ST-elevation myocardial infarction and accepted revascularization of the left anterior descending artery in the second week after discharge. Conclusion: Guillain-Barré syndrome could accompany chest pain and abnormalities on ECG. Meanwhile, it is essential to bear in mind that "GBS-related ECG abnormalities and chest pain" is a diagnosis of exclusion that can only be considered after excluding coronary artery disease, especially when concomitant chest pain, despite being a common presentation of pantalgia, occurs.