Clinical relevance of antibody‐mediated rejection (ABMR) in vascularized composite allotransplantation (VCA) has not been defined. We herein describe a novel type of donor‐specific antibody (DSA) and B‐cell‐associated rejection in hand transplantation. In 2003, a bilateral forearm transplantation was performed on a 42‐year‐old male patient. In 2012, the patient presented with edematous hands and forearms without skin lesions. Punch skin biopsies revealed rejection grade Banff II. Immunohistochemical analysis identified large aggregates of CD20 +  lymphocytes with an architecture resembling lymph nodes. De novo DSA was found at a high level. Steroid treatment was ineffective, but administration of rituximab resulted in complete remission of clinical symptoms, evaporation of B‐cell aggregates, and disappearance of DSA. We herein report the first case of what we suggest is an ABMR in VCA occurring at 9 years after forearm transplantation. Rituximab therapy successfully reversed the event.