To report an association between retinal vein occlusion and increased plasma levels of histidine-rich glycoprotein. Observational case report. A 56-year-old woman presented with sudden and painless decrease of visual acuity of her right eye. Indirect ophthalmoscopy revealed retinal vein occlusion. She had experienced central retinal vein occlusion in this eye 6 years earlier. The patient’s medical history was negative for cardiovascular risk factors. Further investigation into possible causes revealed increased values for histidine-rich glycoprotein. When ordering laboratory tests in patients with retinal vein occlusion to rule out coagulation disorders, increased plasma levels of histidine-rich glycoprotein should be considered in the differential diagnosis. Selective screening may be helpful in identifying retinal vein occlusion patients with thrombophilic defects, especially in young individuals with recurrent retinal vein occlusion in the absence of recognized cardiovascular risk factors.