Purpose: To characterize reticular pseudodrusen, a potential risk factor for late age-related macular degeneration. Design: Retrospective, observational case series. Participants: Fifty-eight eyes of 33 patients with pseudodrusen (20 female). Methods: Consecutive patients with reticular pseudodrusen, diagnosed by their typical appearance and distribution using ophthalmoscopy, the blue channel of color fundus photographs, and near infrared images. The patients were imaged by spectral domain optical coherence tomography (SD OCT), and correlations were made between the near infrared images and the SD OCT images. The SD OCT findings in patients with pseudodrusen were compared with previously reported histologic findings of subretinal drusenoid deposits. The histologic specimens were reevaluated with the additional knowledge of the clinical information. Main Outcome Measures: Spectral domain optical coherence tomography and histologic characteristics of pseudodrusen. Results: The mean age of the 33 patients was 81.7 years. The correlating SD OCT scans showed collections of granular hyperreflective material above the retinal pigment epithelium (RPE), in the subretinal space located primarily between the RPE and the boundary between the inner and outer segments of the photoreceptors (IS/OS boundary). In a more advanced stage, this material formed small mounds that broke through the IS/OS boundary. There were no correlates to the deposits seen under the RPE or in the choroid. These findings were similar in character to previously reported histologic characterization of subretinal drusenoid deposits, which had identified the presence of membranous debris, unesterified cholesterol, and complement within the deposits. Conclusions: Pseudodrusen seen by clinical examination may be subretinal drusenoid deposits seen by histologic examination. This unexpected location suggests that potential pathophysiologic mechanisms on both sides of the RPE need to be taken into account in theories related to the development of age-related macular degeneration. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. © 2010 American Academy of Ophthalmology.