Objective To evaluate prospectively local tumor control and morbidity after fractionated CyberKnife radiosurgery for uveal melanoma unsuitable for ruthenium-106 brachytherapy or local resection. Methods This study includes melanoma a parts per thousand yen7 mm in initial height, or juxtapapillary and/or juxtamacular tumors (height a parts per thousand yen3 mm; posterior tumor margin extending to within 3 mm of optic disk rim and/or fovea). Patients were excluded if they presented evidence of echographic extrascleral tumor extension, neovascular glaucoma, or any form of pretreatment or metastases at baseline. The eye was stabilized by the same ophthalmologist via peribulbar injection of 5 cc 2% lidocaine. CyberKnife radiosurgery was performed delivering a total dose of 60 Gy to the 80% or 85% isodose line in three fractions. The planning target volume (PTV) included the contrast-enhancing lesion on MRI plus a 1-mm margin (no margin on fovea site). Results Five patients with uveal melanoma were treated by this procedure. All patients had serous retinal detachment associated with the tumor. No grade a parts per thousand yen2 acute toxicities were observed. Eight-month follow-up revealed a decrease in tumor thickness in three patients and reattachment of the retina in four. The tumors remained stable in two eyes and an increase in retinal detachment was noted in one eye. Vision improved minimally in two eyes and remained stable in three. Conclusion CyberKnife fractionated radiosurgery seems to be a viable alternative local treatment modality in uveal melanoma with no serious acute side effects. Further follow-up is indicated.