Ocular histoplasmosis syndrome (OHS) is a significant cause of vision loss in young and middle-aged adults. We report here a case of an immunocompetent 37-year-old man who presented fever, malaise, headache, and anterior cervical lymphadenopathy for one week, after which he started to experience a sudden loss in visual acuity of his right eye. Fluorescent angiography and an optical coherent tomography demonstrated the presence of a type II choroidal neo-vascular membrane in the right eye, suggesting a diagnosis of OHS. A peripheral blood sample was tested by nested PCR to detect Histoplasma capsulatum using a set of primers known to amplify a DNA sequence coding for a specific 100-kDa protein of this fungus (Hc100-PCR). The blood sample was Hc100-PCR-positive and sequence analysis showed an identity of 97% with the reference sequence. The patient received intravitreal bevacizumab injection and itraconazol therapy, leading to an improvement in media vision acuity. In this case, the molecular test provided evidence linking the ocular lesions with an earlier infection by H. capsulatum and demonstrated that the Hc100-nested PCR assay is a valuable tool in the diagnosis of histoplasmosis.