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Context Macroenzymes are serum enzymes presenting a higher molecular mass than the corresponding enzymes normally found in physiologic conditions or specific diseases, causing falsely increased total serum enzyme levels. The occurrence of macroenzymes represents a rare event in clinical practice, leading to unnecessary and often invasive additional diagnostic procedures. Macroamylase and macro-creatine kinase belong to this category and may generate diagnostic confusion in the differential diagnosis between acute pancreatitis and acute myocardial infarction. Until now, the association of macroamylase and macrocreatine kinase in the same patient has never been described. Case report A 68-year-old female patient presenting with increased serum levels of creatinine kinase and amylase at admission. Conclusions This article reports the association of macroamylase and macrocreatine kinase in the same patient for the first time.