© 2015 Elsevier Inc. This report presents a falsely incompatible B cell crossmatch by flow cytometry in a lung transplant recipient. The patient was a 35-year-old Caucasian male with end-stage lung disease secondary to cystic fibrosis whose pretransplantation serologic workup did not disclose the presence of anti-HLA class II antibodies by single antigen bead testing. Unexpectedly, crossmatch of recipient sera with pronase-treated donor lymphocytes resulted in antibody binding to B cells only. The positive reactivity was reproducible in pronase-treated autologous B cells. Recipient sera did not react with nontreated donor or autologous lymphocytes. Herein, we describe our approach to this unexpected crossmatch result and consider the implications of false-positive crossmatch results on transplantation.