The present study aimed to characterize the specific pathology and magnetic resonance imaging (MRI) findings observed in patients with leukemia with central nervous system (CNS) lesions, and to determine their value in the management of such patients. Lesions of the CNS were observed during and following treatment of leukemia. The data from stereotactic biopsy-proven pathology (12 patients) and MRI examinations (14 patients) were retrospectively evaluated. Proton-magnetic resonance-spectroscopy was performed in three patients. Factors that predisposed to lesions of the CNS were reviewed from the patient medical records. Among the 14 patients, eight had CNS leukemia, four had a CNS infection and two had a neurodegenerative disorder (one leukoencephalopathy and one glial cell hyperplasia). The clinical diagnosis based on clinical symptoms, signs and MRI features was not consistent with the pathological diagnosis in two patients. In one patient, the clinical diagnosis was a CNS infection; however, the patient's pathological diagnosis was CNS leukemia. In the other patient, the clinical diagnosis was CNS leukemia, but the pathological diagnosis was glial cell hyperplasia. CNS lesions in leukemia have a wide range of causes. Apart from the relapse of leukemia in the CNS, there are treatment-associated neurotoxicities and infections that are caused by immunocompromised states. As numerous leukemia-associated CNS lesions are treatable, early diagnosis is essential.