Different desensitization strategies are available for treating patients with preformed human leukocyte antigen (HLA) antibodies. A highly presensitized heart recipient received immunoadsorption and rituximab therapy. The patient, with end-stage heart failure, was positive only for antibodies of HLA class I (anti-A2, A10, B17), and Luminex platform (One Lambda kit) showed a panel-reactive antibody score of 64%. The patient's serum was tested repeatedly in both complement-dependent cytotoxicity and flow-cytometry crossmatches against cells from different potential organ donors. The results of these crossmatches were positive on flow cytometry when tested with HLA-A2, A10, and B17 but were still negative on cytotoxicity. The patient was treated with a desensitization regimen; this treatment immediately decreased antibody levels of 70% and the patient subsequently received a transplant with donor-specific HLA antibody (HLA-A2). After more than 2 years, graft function remains normal and the clinical status of the patient is stable.