We identified 10 solid organ transplant recipients with a histologic diagnosis of graft-vs-host disease (GVHD). Histologic slides were reviewed, and information on the transplant, HLA match, and blood product transfusion history was obtained. Molecular testing to evaluate the presence of donor lymphocytes (chimerism) was done in 1 case. All patients underwent at least 1 gastrointestinal biopsy; 1 patient also underwent a skin biopsy and 1 patient a liver biopsy; all specimens showed grade I to IV acute GVHD. Six patients had a diagnosis of GVHD within 3 months of blood product transfusion and/or solid organ transplantation, which is the time frame in which GVHD reportedly occurs after solid organ transplantation; 4 patients had a distant history of blood product transfusion or solid organ transplantation. In 1 patient, a molecular technique using the polymorphic marker DIS80 documented donor lymphocytes in the colonic tissue and blood (chimerism). Although histologic findings of GVHD are quite specific, they are not pathognomonic. A GVHD-like histologic pattern can be seen in other conditions such as drug reactions and viral infections. Demonstration of donor lymphocytes in the involved organ helps support the diagnosis of GVHD in questionable cases.