We describe the case of a 35-year-old HIV-positive male of African origin diagnosed with neurotoxoplasmosis and a Nannizziopsis spp. cavitating pulmonary lesion unmasking immune reconstitution inflammatory syndrome (IRIS). The patient presented with headache, left hemiparesis and confusion. MRI of the brain showed two space-occupying lesions in the right basal ganglia and left parietal lobe typical for neurotoxoplasmosis. The patient tested positive for HIV and had advanced CD4 lymphopenia. After commencement of antiretroviral treatment, a CT scan of the chest showed a cavitating lesion in the right upper lobe. The diagnosis of Nannizziopsis spp. fungal infection was confirmed by DNA sequencing on a bronchial wash sample. The patient achieved complete recovery with antiretroviral therapy, standard neurotoxoplasmosis treatment and antifungal treatment with voriconazole for 12 weeks. LEARNING POINTS: AIDS patients at risk of multiple concomitant opportunistic infections present a significant diagnostic challenge.Unusual pathologies should also be considered in addition to the most common opportunistic pathogens, especially in the context of immune reconstitution inflammatory syndrome.