BACKGROUND: Central nervous system (CNS) involvement in diffuse large B-cell lymphoma (DLBCL) is relatively rare, occurring at a rate of approximately 5%. Primary CNS lymphoma (CNS-DLBCL), a subtype of DLBCL, is rare clinically but highly malignant and invasive. Its atypical clinical symptoms and imaging features contribute to a high rate of misdiagnosis and a poor prognosis. Thus, early and accurate diagnosis is imperative for improving the patient's prognosis. Cerebrospinal fluid (CSF) cytology, a rapid and convenient diagnostic method, plays a crucial role in diagnosing intracranial tumors. CASE PRESENTATION: In this instance, the patient presented with nonspecific early symptoms and exhibited atypical imaging findings. A lumbar puncture performed at another hospital yielded a low cell count in the CSF, leading to an incorrect diagnosis. Upon admission to our hospital, CSF cytology identified abnormal cells. A definitive diagnosis of CNS-DLBCL was established utilizing additional diagnostic methods, facilitating targeted treatment. CONCLUSIONS: This case underscores the pivotal role of CSF cytology in rapidly guiding the differential diagnosis of intracranial tumors and underscores the necessity of training laboratory personnel in morphological examination.