Since the introduction of combination antiretroviral therapy (cART), there has been a decrease in the incidence of non-Hodgkin lymphoma among the HIV-infected population and also significantly improved survival rates. We describe a remarkable case of a HIV-infected patient whose large B-cell lymphoma, most likely arising by transformation of a nodal marginal zone lymphoma, completely regressed with the use of cART alone. He remained disease-free for almost 3 years and he finally died from presumed flare up of his lymphoma. There are very few cases of spontaneous regression of lymphomas with cART alone in the HIV population. This is an extreme example of the significance of cART in improving survival in HIV-non-Hodgkin lymphoma and changing the face of the HIV epidemic in general.