Purpose To report on the presence of retinal pigment epithelium (RPE) humps in high myopia, and to describe the distinctive features from pathologic RPE detachments and choroidal neovascularizations (CNVs). Design Retrospective cross-sectional study. Methods Charts and imaging studies of highly myopic patients presenting between September 2015 and February 2017 at a university teaching hospital were consecutively reviewed. All patients underwent spectral-domain optical coherence tomography (OCT). RPE humps were defined as RPE elevations above its physiologic profile, without any evidence of pathologic sub-RPE material. Multimodal imaging was analyzed to assess abnormalities of the RPE and choroid. Results One hundred and ninety-five eyes of 101 highly myopic patients were included. RPE humps on structural OCT were identified in 99 out of 195 eyes (estimated prevalence of 50.8%; 43.8%–57.8, 95% confidence intervals). In all eyes, RPE humps corresponded to large choroidal vessels lifting the RPE. Patchy, diffuse, or CNV-related atrophy was more common in eyes with RPE humps (60.6% vs 34.4%; P <.05). The presence of a large choroidal vessel elevating the RPE and the absence of abnormal material between the RPE and the Bruch membrane were the features distinctive from pathologic RPE detachments and CNVs. Discussion RPE humps were frequently observed in highly myopic eyes and they resulted from the presence of an underlying large choroidal vessel. They are more likely to appear in highly myopic eyes with advanced choroidal atrophy. To prevent unnecessary treatments, they should be distinguished from pathologic RPE detachments and CNVs. © 2017 Elsevier Inc.