Forty‐four related Great Pyrenees dogs were examined ophthalmoscopically. Focal retinal elevations, multiple gray–tan–pink subretinal patches, and discrete areas of tapetal hyper‐reflectivity were seen in 19 dogs, ranging from 13 weeks to 10 years of age. These lesions varied in size from focal spots that were barely visible with the indirect ophthalmoscope to areas that were larger than the optic disc. Complete blood cell counts, serum biochemical profiles, urinalyses, and blood pressure measurements were completed on four affected dogs and all were within normal reference ranges. Photopic and scotopic electroretinography was completed and the a‐wave and b‐wave amplitudes and latencies were similar for affected and age‐matched nonaffected Great Pyrenees and other normal dogs. Electroretinograms that were examined twice during a 3‐year period on three affected adult dogs did not reveal significant progressive deterioration of the a or b‐wave parameters. Fluorescein angiography was completed on four affected dogs of ages 1 (n = 2), 5, and 6 years. These angiograms were repeated in three of these dogs 1 year later. The blood ocular barrier was intact in these dogs but there was blocked choroidal fluorescence. Postmortem examination, light microscopy, scanning and transmission electron microscopy were performed on three affected puppies and two affected adult dogs. These examinations revealed that the lesions in the puppies were limited to bilateral multiple areas of retinal pigment epithelial vacuolation, hypertrophy, and apparent separation from Bruch’s membrane, and multiple serous retinal detachments. The affected adult dogs had focal retinal degeneration and retinal pigment epithelial hypertrophy, hyperplasia and pigmentation. Pedigree analysis and test mating confirm that this condition is inherited, probably as an autosomal recessive trait. This condition develops at ≈ 13 weeks of age and the focal areas of retinal detachment and retinal pigment epithelial vacuolation progress to permanent and stable focal areas of retinal degeneration, and retinal pigment epithelial hypertrophy and pigmentation.