A 55-year-old male complained of right eye blurry vision for 3 days. His best-corrected visual acuity(BCVA) was 0.2 for the right eye and 1.0 for the left eye. Anterior segment and vitreous body examinations of both eyes were normal. Yellowish-white focal lesions in the macula of the right eye were observed and subtly changes of lesions were found along the superotemporal and inferotemporal arcades in the macula two days later. Fluorescein fundus angiography(FFA) revealed slight fluorescent leakage from the lesions in the macula of the right eye, and segmental venous leakage and optic disc hyperfluorescence were observed in both eyes. Indocyanine green angiography(ICGA) demonstrated that the lesions in the macula of the right eye had hypofluorescence at a late stage and spectral domain optical coherence tomography(SD-OCT) imaging of the macula showed focal impairment of the inner segment and outer segment(IS/OS). The blood investigation indicated a positive treponema pallidum hemagglutination assay(TPPA) and a rapid plasma reagin test(RPR) of 1:32. After antisyphilitica treatment for 6 weeks, the yellowish-white lesions had vanished and the BCVA was 1.2 followed by restoration of the IS/OS for the right eye, with an RPR of 1:4. In conclusion, ophthalmologists should alert unilateral focal lesions in the macula may be the first sign of syphilis. Prompt treatment is highly effective in resolving vision. His 55-year-old male complained of right eye blurry vision for 3 days. His best-corrected visual acuity (BCVA) was 0.2 for the right eye and 1.0 for the left eye. Anterior segment and vitreous body examinations of both eyes were normal Yellowish-white focal lesions in the macula of the right eye were observed and subtly changes of lesions were found along the superotemporal and inferotemporal arcades in the macula two days later. Fluorescein fundus angiography (FFA) revealed slight fluorescent leakage from the lesions in the macula of the right eye, and segmental venous leakage and optic disc hyperfluorescence were observed in both eyes. Indocyanine green angiography (ICGA) demonstrated that the lesions in the macula of the right eye had hypofluorescence at a late stage and spectral domain optical coherence tomography ( SD-OCT) imaging of the macula showed focal impairment of the inner segment and outer segment (IS / OS). The blood test indicated a positive treponema pallidum hemagglut ination assay (TPPA) and a rapid plasma reagin test (RPR) of 1:32. After antisyphilitica treatment for 6 weeks, the yellowish-white lesions had vanished and the BCVA was 1.2 followed by restoration of the IS / OS for the right eye , with an RPR of 1: 4. In conclusion, ophthalmologists should alert unilateral focal lesions in the macula may be the first sign of syphilis. Prompt treatment is highly effective in resolving vision.