Studies suggest a relationship of manic behavior and bipolar disorder (BD) with behavioral variant frontotemporal dementia (bvFTD). The nature of this relationship is unclear. This report presents a patient with initial manic behavior as the main manifestation of familial bvFTD from a novel progranulin (GRN) mutation. In contrast, there are other reports of a long background of BD preceding a diagnosis of bvFTD. A review of the literature and this patient suggest that manic symptoms result from damage to right frontotemporal neural structures from longstanding BD, as well as from bvFTD and other focal neurological disorders. In addition, there is a subgroup of patients with a probable genetic predisposition to both BD and bvFTD.