Abstract: Trisomy 3 has been previously reported in association with T-cell lymphomas and less commonly in different types of non-Hodgkin B-cell lymphomas. Trisomy 3 has also been reported in two cases of pediatric post-transplant lymphoproliferative disorder (PTLD). We present comprehensive clinicopathologic review of two pediatric patients with cardiac and liver/intestinal allografts that developed polymorphous PTLD characterized by trisomy 3. Both patients had EBV viremia and EBV was positive in tissue by EBER in situ hybridization. Using karyotype analysis and fluorescence in situ hybridization, we identified trisomy 3 in both patients. Both patients responded to treatment and are now free of the PTLD. Trisomy 3, an uncommon cytogenetic finding in PTLD, may be a recurrent cytogenetic if confirmed in a larger study of pediatric PTLD’s. Further clinical follow up might help stratify significance of trisomy 3 as a prognostic factor.