Background To evaluate choroidal thickness, ganglion cell complex (GCC) and photoreceptor outer segment length were measured in patients with breast cancer undergoing tamoxifen therapy, using spectral-domain optical coherence tomography (SD-OCT); results were compared with those for normal eyes. Methods Forty-four patients with breast cancer, undergoing tamoxifen therapy, and 41 healthy controls were included in this prospective, comparative study. All participants underwent a complete ophthalmologic evaluation and SD-OCT. Subfoveal, nasal (nasal distance to fovea 500, 1000, 1500 μm), and temporal (temporal distance to fovea 500, 1000, 1500 μm) choroidal thickness measurements were performed using the enhanced depth imaging mode of SD-OCT. Using an Early Treatment Diagnostic Retinopathy Study (ETDRS) circle at the macular level, the automated retinal segmentation software was applied to determine the thickness of the GCC. The photoreceptor outer segment (PROS) length was determined manually, as the distance from the inner surface of the ellipsoid zone to the inner surface of retina pigment epithelium. Results The mean choroidal thickness was statistically greater in the tamoxifen group than controls in all quadrants ( p < 0.001 for all quadrants). Of all tamoxifen users (44 eyes of 44 patients), 33 eyes (75%) had UCP. Pachychoroid pigment epitheliopathy (PPE) was detected in five tamoxifen-group patients (11.3%). Patients with PPE in one eye had UCP in the fellow eye. Central serous chorioretinopathy findings were observed in one patient. Tamoxifen users had statistically lower GCC thickness in all inner rings of the ETDRS inlay and in the nasal outer ring only ( p = 0.027, 0.002, 0.002, 0.001, and 0.030, respectively). No statistically significant difference in mean subfoveal PROS length was found between the groups. Conclusions SD-OCT provides valuable information for identifying structural changes and evaluating ocular findings in patients receiving tamoxifen therapy. Increased choroidal thickness, PPE and thinning GCC were detected in tamoxifen users. These OCT findings may be an early indicator of retinal toxicity for patients undergoing tamoxifen therapy in the follow-up period. Keywords tamoxifen retinopathy, choroidal thickness, ganglion cell complex, PROS, spectral-domain optical coherence tomography