Acute B19 virus infection is classically associated with a widespread benign and self-limiting childhood rash illness, known as erythema infectiosum (EI) or fifth disease. The clinical presentation associated with B19 infection may vary greatly, ranging from benign forms of arthralgias to life-threatening conditions, depending on age and immunologic status. A case of polymyalgia rheumatica (PMR) in a 74-years-old woman affected by B19 virus infection is reported here, presenting with evening low-grade fever, shoulder and pelvic girdle arthralgia and functional impairment. A comprehensive review of the literature showed that B19 virus has been hypothetically implicated as the causative or precipitating agent of several autoimmune and rheumatic diseases, including PMR. Some molecular mechanisms underlying the autoimmune phenomena have been described, involving the inflammatory response due to cytokine activation, the formation and deposition of immune complexes and molecular mimicry mechanisms. Nowadays, the reports in the literature, which have focused on the possible role of Parvovirus B19 in the pathogenesis of PMR, are few and discordant. Therefore, further and more in deep investigations are needed, hopefully leading to a final consensus between researchers.