We present a case of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) harboring the N279K mutation in the MAPT gene from the family known as pallido-ponto-nigral degeneration (PPND). This 49-year-old man was followed for 17 years. He presented at age 41 years with left leg stiffness and en-bloc turning. During the course of his illness he developed a constellation of symptoms including parkinsonism, pyramidal signs, vertical gaze palsy, dysphagia, dystonia, personality and cognitive dysfunction, weight loss and mutism. Gross neuropathological examination showed mild atrophy of the cerebral cortex, hippocampal formation, amygdala, thalamus, subthalamic nucleus and depigmentation of the substantia nigra. Microscopy revealed neuronal loss and gliosis in the same regions. Tau immunohistochemistry showed pretangles, numerous threads, grain-like structures and oligodendroglial tau-positive inclusions ("coiled bodies"). In the spinal cord the tau pathology was more abundant in gray than white matter. Pretangles and threads were present in the anterior and, to a lesser extent, in the posterior horns. FTDP-17 should be suspected in patients with a history of familial parkinsonism combined with behavioral and cognitive changes, onset before age 65 years and an aggressive clinical course.