Cancer incidence after solid organ transplantation has been steadily increasing due to multiple reasons, including improved survival of transplant recipients and exposure to prolonged immunosuppression. Defining neoplasm cell of origin in patients with solid organ transplants may be important for future improvement of donor selection criteria, patient and other recipient counseling, as well as for treatment tailoring. There are several methods by which determining cancer cell of origin can be accomplished. We describe a patient who was diagnosed with extensive stage small cell lung cancer 9 months after he had received double lung transplant. Origin of malignancy was defined by means of PCR-based assay that compared DNA isolates from the diagnostic small cell carcinoma specimen to explanted lung tissue as well as to non-malignant donor lung tissue. The results supported donor derived malignancy—information that was relayed to patient as well as all other centers where organ transplants from the same donor were performed.