In this prospective clinical study, we treated 8 patients (8 eyes, 11 tumors) of macular retinoblastoma with chemotherapy alone, with the aim of avoiding visual loss because of retinal damage by radiation or adjuvant therapy and to assess their final visual outcome. The mean basal dimension of the tumor was 5.0 ± 2.6 mm and the mean height was 2.9 ± 1.3 mm. The fovea was involved in 4 patients (50%) and foveal detachment was present in 3 patients (37.5%). All the patients required less than 6 cycles for tumor control. Four patients (50%) obtained visual acuities ranging from 20/25 to 20/200. Two patients (25%) could gain visual acuity of 20/20. The mean follow-up of patients was 3.24 ± 0.9 years (range 2–5). No patient developed recurrence or metastatic disease. In conclusion, recent trends for ocular salvage have favored chemoreduction followed by focal therapy for the treatment of retinoblastoma. This study supports the consideration of chemotherapy alone as the primary treatment in eyes with macular retinoblastomas, under close supervision, with satisfactory visual outcome.