A patient in their late 50s came for routine ophthalmologic evaluation. On examination, the patient exhibited bilateral, diffuse, atrophic patches on the iris with posterior synechiae and deep pitted scars (moth-eaten appearance), which had been present since childhood (Figure). In addition, multiple pitted scars were noted on the patient’s face as a result of presumed smallpox infection in childhood. Near-infrared autofluorescence of the iris showed an altered petaloid pattern in the pupillary zone and minimal autofluorescence in the deep radial troughs with altered reticular pattern in the ciliary zone. We performed an anterior-chamber paracentesis and sent the aqueous humor for polymerase chain reaction testing for herpes simplex virus types 1 and 2, varicella-zoster virus, rubella virus, and cytomegalovirus, the results of which were nonreactive. A polymerase chain reaction sample for smallpox could not be performed due to limited access to such an assay. Thus, the lesions on the iris were presumed to be the sequelae of smallpox infection (vitiligo iridis); however, this cannot be proven. The other etiologies for iris depigmentation, such as pigment dispersion syndrome, pseudoexfoliation, and active uveitis, were ruled out in this patient.