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Abstract Background The International System for Reporting Serous Fluid Cytopathology (TIS) was recently proposed. We retrospectively applied TIS recommendations for reporting the cytological diagnosis of serous effusions and reported our experience. Methods All the serous effusions from January 2018 to September 2021 were retrieved from the database. Recategorization was performed using the TIS classification, the risk of malignancy (ROM) was calculated for each TIS category. In addition, on the basis of the original TIS classification, we further subdivided the TIS category IV (suspicious for malignancy, SFM) into 2 groups (IVa and IVb) according to cytological characteristics (quality and quantity) to explore the necessity of SFM subclassification. The performance evaluation was carried out using different samples (pleural, peritoneal and pericardial effusions) and preparation methods (conventional smears, liquid-based preparations and cell blocks). Results A total of 3633 cases were studied: 17 (0.5%) were diagnosed as ‘nondiagnostic’ (I, ND), 1100 (30.3%) as ‘negative for malignancy’ (II, NFM), 101 (2.8%) as ‘atypia of undetermined significance’ (III, AUS), 677 (18.6%) as ‘suspicious for malignancy’ (IV, SFM), and 1738 (47.8%) as ‘malignant’ (V, MAL). The ROMs for the categories were 38.5%, 28.6%, 52.1%, 99.4% and 100%, respectively. The ROM for SFM was significantly higher than that for AUS (P