We report two cases of histoplasmosis occurring in human immunodeficiency virus-positive patients who immigrated to Italy, and focus our attention on the clinical features and therapeutic aspects, with particular emphasis on secondary prophylaxis. The patients had comparable human immunodeficiency virus baseline parameters, but had a completely different compliance over therapeutic regimens. The two patients were followed in two different city hospitals of our region, Padua and Verona, and the diagnosis was made on the basis of instrumental, histologic, and microbiologic findings. One of them was treated with corticosteroids because of nephrotic syndrome.