A six-year-old girl with non-Hodgkin's lymphoma who was treated with both intravenous (IV) and intrathecal (IT) methotrexate and developed brain damage secondary to the cytostatic drug is described. This patient displayed hypertension, hypothermia/hyperthermia, lethargy, deterioration and coma as clinical findings, and bilateral, focal white matter hyperintensities in the occipital lobes were seen in her magnetic resonance imaging (MRI). Treatment-related leukoencephalopathy is one such adverse effect of IT methotrexate administration on the central nervous system and usually appears in a generalized form.