PTLD is a serious complication in patients following solid organ or bone marrow transplantation (BMT) with a high mortality rate after conventional therapies. With pathology ranging from plasmacytic hyperplasia to monomorphic PTLD, identifying specific sites of disease for definitive diagnosis can be challenging. We examined the role of PET scanning in the staging and follow-up of PTLD. We retrospectively reviewed all patients treated for PTLD at the University of Minnesota from 2001–2006 who also underwent PET scans. Pathology was confirmed by a hematopathologist. PET scans were reviewed by a nuclear medicine radiologist. 21 patients with PTLD had PET scans at diagnosis or relapse. 20/21 of these PET scans were available for review. In these 20 patients, the type of transplant was lung(4), kidney/pancreas(5), kidney(4), small bowel(1), BMT(2), liver(2), heart/lung(1), and lung/kidney(1). Histology was polymorphic PTLD (n=1), diffuse large B-cell lymphoma (DLBCL) (n=12), DLBCL/polymorphic PTLD (n=2), DLBCL/plasmacytic PTLD (n=1), anaplastic large cell lymphoma (n=1), and mixed cellularity Hodgkin lymphoma (n=1). The median time from transplantation to PTLD diagnosis was 66 months (range, 4–192 mos). At diagnosis, stage of disease was I(3), II(6), III(3), IV(6) and two patients had primary central nervous system lymphoma (PCNSL). 16 patients had extranodal involvement. 17/20 patients had PET scans for staging at the time of diagnosis. The two patients with PCNSL and 1 patient with only bone marrow involvement after complete surgical resection of a bowel lesion were PET negative at the time of diagnosis. All of the remaining patients with measurable disease by CT scan were PET positive at diagnosis. The median maximum standard uptake value (SUV) was 8.8 (range 3–30). 14/20 patients had one or more PET scans following treatment. 10 patients had a complete response with both negative PET and CT scans following therapy. 4 patients had measurable disease by both CT scan and PET scan (2 persistent disease, 1 partial response, 1 relapsed disease). The two patients with persistent disease died. The patients with a partial response and relapsed disease received additional therapy, had a complete response with a negative follow-up PET scan, and currently remain in complete remission at 16 mos and 12 mos, respectively. Of the 10 patients with complete responses documented by PET scan, 7 patients remain in complete remission for a median of 11 mos (range 5–50 mos). 3 patients relapsed shortly thereafter at 1, 4, and 5 months after PET scan. At the time of relapse, PET scan confirmed disease. On each occasion in which there was measurable disease by CT scan at the time of relapse, the PET scans were positive with median maximum SUV 6.8 (range 2.2–10.8). All biopsy confirmed sites of PTLD demonstrated uptake on PET scan, regardless of underlying histology. Due to the small number of patients, it was not possible to correlate SUV uptake with histologic subtype. These findings suggest that PET scans have a role in the staging and follow-up of PTLD. PET scans can identify sites of disease. Maximum SUV may vary at the time of presentation. Regardless of the underlying histology, PET scans are useful in the management of this aggressive disease.