FDG PET imaging is generally not useful for prostate cancer. Nevertheless, incidental intense FDG uptake in the prostate warrants further evaluation to assess for prostatic malignancy. We report a case where intense FDG uptake was incidentally noted in an enlarged prostate on FDG PET/CT scan performed for a large left hilar/mediastinal mass (that was also intensely FDG avid along with several additional FDG-avid lesions elsewhere). Biopsy of the prostate and mediastinal lesions revealed large B-cell non-Hodgkin lymphoma at both sites. Serial FDG PET/CT imaging in this patient revealed that the prostatic lymphomatous lesions showed a slower and incomplete response to chemotherapy compared with other sites of lymphomatous involvement (that showed a rapid and complete response to chemotherapy) in the same patient.