The incidence of cancer is higher in transplant patients than in the normal population, mostly due to the assumption of immunosuppressants able to reduce the possibility of rejection. In addition, immunocompromised patients have a greater susceptibility to EBV, HPV and HIV, infectious agents that by themselves may favor the onset of malignancies. Post-transplant lymphoproliferative diseases (PLDs) are among the most frequent neoplasms in transplant patients which like other aggressive neoplasms may be identified by the [18f] fluoro-D-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). We evaluated the clinical use of FDG-PET/CT in detecting PTLDs and other neoplasms performed at the lowest clinical or laboratory suspicion of malignancy in 127 consecutive subjects who underwent heart transplantation. A SUV>4 more confirmed the suspect of malignancy and induced us to further investigations. Of the 127 transplant subjects who underwent FDG-PET/CT, 64 showed a SUV value >4. Of these 64, 8 had PTLDs, 49 other neoplasms (urinary tract tumors, thyroid cancer, HPV cancer related, Kaposi' sarcoma and EBV related head and neck neoplasms) and 7 patients with chronic non-neoplastic inflammatory diseases. In the present study, FDG-PET/CT examination was of great use for an early identification and for an early treatment of PTLDs and other neoplasms.