Numerous complications can be observed in the post-transplant period among recipients of hematopoietic stem cells including graft-versus-host disease (GVHD), which is associated with significant morbidity and mortality. On the other hand, graft versus tumor (GVT) effect is a well-described phenomenon in patients with hematologic malignancies and has also been reported in renal cell cancer, ovarian cancer, breast carcinoma, and melanoma. We describe spontaneous regression of a cutaneous invasive squamous cell carcinoma and multifocal atypical intraepidermal proliferations in a patient with chronic graft-versus-host disease following initiation of extracorporeal photopheresis (ECP). This observation raises questions regarding the GVT in cutaneous neoplasms and potential immunomodulatory effects of ECP.