Abstract: Objective: To investigate the application of two immunocytochemical staining methods in the diagnosis of cerebrospinal fluid metastatic lung adenocarcinoma. Methods: From January 2016 to December 2023, 11 patients with a history of lung adenocarcinoma and cerebrospinal fluid metastasis were collected for cerebrospinal fluid cytology. The control group included 11 cases of metastatic lung adenocarcinoma in cerebrospinal fluid stained with hematoxylin and eosin or Papanicolaou staining, and the experimental group included the re-prepared or faded samples of the corresponding control group for immunocytochemical staining. The clinical data, cytological morphology, diagnostic methods and immunocytochemical staining results of the 11 cases were analyzed. Results: In the control group, several atypical cells were observed in clusters or single cells scattered, with moderate to abundant cytoplasm, large and dark nuclei, and some cells had obvious nucleoli. In the experimental group, the metastatic lung adenocarcinoma was confirmed by TTF-1 and NapsinA immunocytochemical staining. Conclusion: The prognosis of patients with leptomeningeal metastasis from lung adenocarcinoma is extremely poor. The definite diagnosis of cerebrospinal fluid cytology is of great significance for clinical practice. When the amount of cerebrospinal fluid specimens is limited and there are only a small number of atypical cells, immunocytochemical staining after re-preparing or fading can make a definite diagnosis to assist clinical treatment.