A 58-year-old man with large penile wound and enlarged regional lymph node was suspected of having disseminated penile cancer. FDG PET/ CT for primary staging showed high FDG uptake on penis and in several enlarged lymph nodes. However, biopsies revealed no signs of malignancy, but ulceration, inflammation, fibrosis, and spirochetes. Furthermore, Wassermann test was positive. The patient was then treated for syphilis. To our knowledge, this is the first report on FDG PET/CT in a patient suspected of having penile cancer that turned out to be syphilis. Thus, syphilis can be added to the list of benign pitfalls in FDG PET/CT.