Post-transplant malignancy of donor origin is a rare complication of organ transplantation, most likely transmitted as micrometastases within the parenchyma of the donor organ or from circulating tumor cells contained within the organ. Patient survival is dependent upon early diagnoses, and differentiation of the malignancy as of donor or recipient derivation is important in developing a treatment modality. The utilization of fluorescent in situ hybridization chromosome analysis and DNA sequence analysis of the tumor cells can assist in this determination. This case report describes the management of donor transmitted malignant melanoma in a liver graft recipient and a review of the current literature.