Atypical mycobacterial infections are frequent, late complications of human immunodeficiency virus infections and may have a variety of clinical manifestations.We describe a patient with end-stage acquired immune deficiency syndrome and disseminated atypical mycobacteriosis caused by Mycobacterium avium-intracellulare complex, with prominent iris nodules as the initial manifestation of a unilateral localized panophthalmitis. Acid-fast bacilli were identified cytologically from the iris nodule and aqueous aspirations. Topical, intracameral, and systemic treatments were used, but the infection progressed and enucleation was performed to avoid the impending scleral rupture. Histopathologic studies revealed an anterior panophthalmitis, with inferior scleral rupture due to acid-fast bacilli in the eye. Mycobacterium avium-intracellulare complex has been described as a cause of endophthalmitis in immunocompromised patients but, to our knowledge, this is the first report of a patient with iris nodules.