Dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy in children. Heart transplantation is considered standard therapy in dilated cardiomyopathy with end-stage heart failure. We present a case of a 15-year-old patient diagnosed with DCM in the neonatal period, who underwent heart transplantation for end-stage heart failure. Despite the use of induction therapy, the endomyocardial biopsy performed at two weeks post-transplant revealed mixed moderate cellular (2R) and humoral (pAMR2) allograft rejection. Aggressive rejection treatment was initiated with good outcome. Besides endomyocardial biopsy, advanced echocardiography can also be a valuable noninvasive tool for rejection assessment.