We report the case of a young patient with an ischemic stroke due to a paradoxical embolism through a giant isolated pulmonary arterio-venous fistula and review the literature of similar cases. We argue that the use of contrast transcranial Doppler (c-TCD) may well help in redressing the likely situation of underdiagnosis of this condition. C-TCD is reliable and sensitive in the diagnosis of right-to-left shunt and allows us to suspect pulmonary arterio-venous fistula as the underlying mechanism. Furthermore, the qualities of non-invasiveness, ease of use, precision, reliability and inexpensiveness of c-TCD make it the ideal tool for checking the success of surgical or endovascular treatment and subsequent follow-ups.