The presence of macroamylasemia should be considered in the differential diagnosis of hyperamylasemia associated with acute abdominal pain, with suspect of pancreatitis. This uncommon and poorly known abnormality is defined as a blinding of serum amylase to certain proteins forming a circulating macrocomplex which prevents renal clearance of serum amylase. Two clinical cases as well as a review of this rare entity are here reported.