Hematological evaluation to explain indirect hyperbilirubinemia in a boy with cardiac arrhythmia showed the presence of PIEZO1-related hereditary xerocytosis (HX) [c.6008C>A (p.Ala2003Asp) variant] presenting with compensated hemolytic anemia and splenomegaly. PIEZO1 expression is not limited to erythrocytes and can also be found in other types of cells. It has been shown very recently that PIEZO1 is expressed in cardiomyocytes and chemically prolonging PIEZO1 activation results in cardiac arrhythmias. Since no other causative variants were detected in genes previously associated with cardiac arrhythmias, the arrhythmia was attributed to the PIEZO1 variant underlying HX. Arrhythmias can be fatal and we recommend that cardiac evaluation be part of the examination in patients with PIEZO1-related HX.