PURPOSE. We reported an unusual appearance of fundus autofluorescence (FAF) associated with NR2E3-p.G56R-linked autosomal dominant retinitis pigmentosa (ADRP). METHODS. Patients were enrolled among three generations in a Swiss family. Molecular diagnosis identified a c.166G > A (p.G56R) mutation. Ophthalmic examination included fundus photography, FAF near-infrared autofluorescence (NIA), optical coherence tomography (OCT), and visual fields (VF). RESULTS. Fundus examination revealed a wide range of features from unremarkable to attenuated arterial caliber, clumped and spicular pigment deposits in the mid-periphery and optic nerve pallor. FAF showed a double concentric hyperautofluorescent ring: an inner perimacular ring that tended to be smaller in older patients, and an outer ring located along the vascular arcades, which appeared to extend over time toward the periphery and eventually became hypoautofluorescent. The inner and outer hyperautofluorescent rings were seen both on NIA and FAF at a similar localization. There was also a spatial correspondence between the loss of photoreceptor inner segment and outer segment junction on OCT and the area delimited by both double FAF and NIA rings. VF showed either mid-peripheral annular scotoma or constricted visual field loss in advanced cases, correlating with dystrophic nonfunctional retinal regions demarcated by the hyperautofluorescent annuli. A double ring of hyperautofluorescence was observed in all but one patient of two additional families, but not in patients harboring mutations in other ADRP genes, including PRPF3, RHO, RP1, PRPH2, PROM1, and CTRP5. CONCLUSIONS. The presence of a double concentric hyperautofluorescent ring of FAF may represent a highly penetrant early phenotypic marker of NR2E3-p.G56R-linked ADRP. (Invest Ophthalmol Vis Sci. 2012; 53:4754-4764) DOI: 10.1167/iovs.11-8693