AbstractIntroductionMonitoring for graft rejection is a fundamental tenet of post‐transplant follow‐up. In heart transplantation (HT) in particular, rejection has been traditionally assessed with endomyocardial biopsy (EMB). EMB has potential complications and noted limitations, including interobserver variability in interpretation. Additional tests, such as basic cardiac biomarkers, cardiac imaging, gene expression profiling (GEP) scores, donor‐derived cell‐free DNA (dd‐cfDNA) and the novel molecular microscope diagnostic system (MMDx) have become critical tools in rejection surveillance beyond standard EMB.MethodsThis paper describes an illustrative case followed by a review of MMDx within the context of other noninvasive screening modalities for rejection.ConclusionsWe suggest MMDx be used to assist with early detection of rejection in cases of discordance between EMB and other noninvasive studies.