We present a case of a 59-year-old male diagnosed with polycythemia vera (PV) for many years, who presented with a relatively abrupt onset of heavy constitutional symptoms, including fatigue, night sweats, and a 10% weight loss over 6 weeks. Despite the known initial diagnosis of PV, the presence of profound B-symptoms prompted further investigation. A positron emission tomography/computed tomography (PET/CT) scan with 18F-Fluorodeoxyglucose ([18F]FDG) was performed to exclude malignant diseases. The [18F]FDG PET/CT revealed intense metabolic activity in the bone marrow of the proximal extremities and trunk skeleton, as well as a massively enlarged spleen with increased metabolic activity. Histopathologically, a transformation to myelofibrosis was revealed on a bone marrow biopsy. The case intends to serve as an exemplification for [18F]FDG PET/CT in PV with transformation to myelofibrosis (post-PV myelofibrosis).