Background: Major improvements in cancer therapies have significantly contributed to increased survival rates of Hodgkin lymphoma (HL) survivors, outweighing cardiovascular side effects and the risks of radiation-induced heart disease. Non-invasive screening for coronary artery disease (CAD) starting five years after irradiation is recommended, as plaque development and morphology may differ in this high-risk population. Due to rapid plaque progression and a possibly higher incidence of non-calcified plaques, coronary artery calcium scoring may not be sufficient as a screening modality in HL survivors treated with thoracic radiotherapy. Case summary: A 42-year-old man with a history of HL treated with thoracic radiotherapy presented at the emergency department 20 years after cancer treatment with an ST-elevation myocardial infarction, in the absence of cardiovascular risk factors, for which primary percutaneous coronary intervention of the left anterior descending artery was performed. Four months prior to acute myocardial infarction, invasive coronary angiography only showed wall irregularities. Two years earlier, the Agatston calcium score was zero. Discussion: In HL survivors treated with thoracic radiotherapy, a calcium score of zero may not give the same warranty period for cardiac event-free survival compared to the general population. Coronary computed tomography angiography can be a proper diagnostic tool to detect CAD at an early stage after mediastinal irradiation, as performing calcium scoring may not be sufficient in this population to detect non-calcified plaques, which may show rapid progression and lead to acute coronary syndrome. Also, intensive lipid-lowering therapy should be considered in the presence of atherosclerosis in this patient population.