In the book Curationum medicinalium Centuria septima (1566) of the Portuguese physician Amatus Lusitanus (1511-1568) a curious clinical case is reported concerning a 3 year-old girl from Limoux (Aude, Southern France) affected by ocular filariasis with the worm spontaneously emerging from the eye. On the basis of the description and localisation of the parasite, and of the locality where it was observed, the nematode might be identified as Dirofilaria repens, the causative agent of canine and human dirofilariasis in the Old World. The case was reported by Ulysse Aldrovandi (1522-1605) in his book De animalibus insectis (1602) with a commentary. According to the text of Lusitanus and to Aldrovandi's commentary, it would appear that both authors had observed additional similar cases, the former referring to ocular and the latter to mammal localisations. If this identification is correct, the zoonosis may have existed in Southern France and Italy for 400 years and the report by Lusitanus may represent the first human case of dirofilariasis published in the world.