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Graft-versus-host disease (GVHD) is rare complication after simultaneous pancreas-kidney transplantation (SPK). Here, we present a rare case of GVHD that developed in a SPK recipient. A 38-year-old female patient with end-stage renal disease due to type 1 diabetes mellitus underwent SPK from a deceased female donor. Four months after transplantation, she was readmitted with fever and abdominal pain and computed tomography revealed a retroperitoneal abscess. While being treated for the retroperitoneal abscess by percutaneous drainage and antibiotics, the patient developed skin rash and diarrhea. A skin biopsy performed at the time showed vacuolization and peri-venular lymphocytic infiltration compatible with GVHD. High-dose steroids resulted in complete remission of GVHD, and the patient was discharged after 2 weeks of treatment. This case demonstrates that early diagnosis of GVHD followed by timely treatment may led to a favorable outcome, and cautions that GVHD can occur in SPK patients.