A pretransplant positive cross-match is a contraindication for kidney transplantation, unlike in liver transplantation (OLT). In combined liver kidney transplantation (LKT) it is hypothesized that liver can protect kidney from rejection. We report the case of a 35-year-old woman on renal replacement therapy with gastrointestinal tract compression due to a hematoma following spontaneous liver rupture (May 2004). She was affected by amyloidosis, treated with a bone marrow autotransplantation (2001). The liver rupture was surgically untreatable, so an LKT was proposed. Panel-reactive antibody was 80% to 100% (complement dependent cytotoxicity) with specific anti-HLA antibodies (enzyme-linked immunosorbent assay). A compatible donor was found (July 2004). The cross-match before LKT was positive for B and T cells (score 8): an emergency OLT was performed. Immediately after liver reperfusion the cross-match result was less positive (6) for T cells. After 6 hours it was negative for T and slightly positive for B cells (4): the kidney was transplanted. The immunosuppressive therapy was: alemtuzumab, steroids, and tacrolimus. Renal function immediately recovered. On day 7 a rejection episode was successfully treated by increasing steroids (intravenous bolus). At discharge hepatic and renal function were normal (creatinine 1 mg/dL). They are stable after 1 year. This case showed LKT efficacy even in complex immunological situations. Many immunological mechanisms, still not defined, are hypothesized about the protective role of the liver. This case confirmed experimental data that highlighted that in vivo in humans a cross-match can change from positive to negative after OLT giving highly sensitized patients the possibility for LKT.