Background: The aim of this case report is to describe the clinical presentation and imaging features of a patient with optic nerve leukaemic infiltration as the first site of relapse after complete response to systemic treatment. Materials and methods: We report the case of a 23-year-old man with history of acute lymphoblastic leukaemia (ALL) in complete remission. Six months later, the ocular examination revealed decreased visual acuity. Fundus examination showed a pale optic disk with blurred margins and multiple flame-shaped and dot and blot retinal haemorrhages in his left eye. A diagnosis of leukaemic infiltration to the optic nerve was made by magnetic resonance imaging (MRI). Cytological analysis of the cerebrospinal fluid did not show any abnormal cells or blasts. Results: A course of oral corticosteroid therapy was prescribed and 20 Gy of radiation was administered to the whole brain including the left orbit. Vision was improved dramatically in the left eye. Isolated optic nerve relapse of leukaemic infiltration is of paramount importance to early diagnosis, as vision can be saved if treatment with orbital radiotherapy is initiated promptly.