Background <p>Low-dose tamoxifen use may cause degenerative changes progressing to full-thickness macular holes, mimicking other degenerative causes for macular holes instead of well-known features of tamoxifen retinopathy. The aim of this report is to present a case of bilateral refractory macular holes related to tamoxifen use and full anatomic restoration of the fovea with autologous retinal graft.</p> Case presentation <p>A 35-year-old female presented with decreased vision in both eyes and was initially diagnosed with a macular hole in the left eye, followed by a subsequent diagnosis in the right eye. Standard internal limiting membrane (ILM) peeling with gas endotamponade for the left eye and inverted ILM flap with gas endotamponade for the right eye both failed to close the macular hole. Therefore, autologous neurosensory retinal grafting was performed for refractory macular holes in both eyes. She was not receiving tamoxifen at the time of presentation; however, she had previously undergone tamoxifen treatment for breast cancer. During the postoperative period, full reconstitution of the ellipsoid zone and the external limiting membrane, as well as foveal pit formation, were achieved with a dramatic increase in visual acuity.</p> Conclusions <p>Autologous retinal grafting may be an effective and safe surgical approach not only for macular holes secondary to posterior hyaloid-related traction but also for the management of refractory degenerative macular holes secondary to drug side effects. This approach achieved excellent functional outcome and successful anatomical improvement, as demonstrated on longitudinal optical coherence tomography scans.</p>