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Dientamoeba fragilis (D. fragilis) is an intestinal parasite frequently detected in humans with abdominal pain and diarrhoea, but it is also commonly found in asymptomatic subjects. Hence its clinical relevance is often disputed. The introduction of polymerase chain reaction (PCR) is a versatile and sensitive diagnostic technique for the detection of intestinal parasites, and in some Western world countries PCR has almost completely replaced microscopic diagnostics. PCR has however resulted in an increase in the number of D. fragilis-positive patients. The disputed pathogenic nature of this intestinal parasite and an apparent increase in the incidence of patients with positive PCR results have renewed the discussions between clinicians and microbiologists on how to deal with an infected patient. Moreover, treatment guidelines differ throughout the world which makes it difficult for clinicians to choose an optimal therapeutic regimen.