Leishmaniasis is emerging as a common and serious opportunistic infection in HIV-infected patients in endemic areas (such as Mediterranean countries), and may occur with various clinical presentations, ranging from typical visceral forms to atypical cases, including cutaneous disease. Although pentavalent antimony compounds have been the mainstay of antileishmanial treatment for half a century, new drugs seem today reliable, including liposomal amphotericin B and pentamidine isethionate. However, the most effective therapy is still unknown. An HIV-infected i.v. drug abuser patient with a very uncommon disseminated cutaneous leishmaniasis, following an initial visceral disease, is described. Primary and recurrent visceral forms of protozoan infection have been treated with liposomal amphotericin B, while pentamidine isethionate was successfully employed as treatment for subsequent cutaneous relapse and as secondary prophylaxis.