Abstract: Objective To evaluate the value of malignant serous cavity effusion cell blocks in the application of molecular pathological diagnosis. Methods Tumor cells were collected and embedded into cell blocks through stratified centrifugal from 85 cancer patients with malignant serous cavity effusion， then were detected by immunohistochemistry， fluorescence in situ hybridisation（FISH） and gene sequencing methods. Results The tumor cells of cell block section were rich and remained histological structures. Immunohistochemistry staining could assist diagnosis and tumor parting. FISH and gene sequencing could provide gene amplification and mutation situation. Ten caces of EGFR gene amplification and 8 caces of EGFR gene mutation were observed in 30 non-small cell lung cancer samples. Conclusion Malignant serous cavity effusion cell blocks are useful for the diagnosis and determing the primary source of tumor， which can instruct targeted therapy.