BackgroundThe International System for Reporting Serous Fluid Cytopathology (ISRSFC) was introduced globally in 2019 in response to the absence of a standardized reporting system for serous fluid cytology. This study presents experiences implementing this system across three distinct hospitals in Taiwan.MethodsA total of 6177 serous fluid specimens in three hospitals in Taiwan between 2018 and 2020 were retrospectively reviewed and reclassified according to the ISRSFC. Cytohistological correlation and chart review were further performed to investigate etiologies and risks of malignancy (ROMs).ResultsReclassification showed that 34 (0.7%) of 4838 pleural effusions were nondiagnostic (ND), 4086 (84.5%) were negative for malignancy (NFM), 201 (4.2%) were atypia of undetermined significance (AUS), 92 (1.9%) were suspicious for malignancy (SFM), and 425 (8.8%) were malignant (MAL). The 1231 ascites cases contained 13 (1.1%) ND, 1004 (81.6%) NFM, 53 (4.3%) AUS, 31 (2.5%) SFM, and 130 (10.6%) MAL specimens. In pleural effusions, the ROM was 2.9% for ND, 14.0% for NFM, 52.2% for AUS, 85.9% for SFM, and 95.1% for MAL. In ascites, it was 15.4% for ND, 19.1% for NFM, 52.8% for AUS, 83.9% for SFM, and 92.3% for MAL. In pericardial effusions, it was 0.0% for ND, 11.6% for NFM, 30.8% for AUS, 100.0% for SFM, and 95.2% for MAL. Different effusions' most common benign and malignant etiologies were also disclosed.ConclusionsThese multi‐institutional data have determined the diagnostic usefulness of the ISRSFC, which provides pathologists and physicians with invaluable assistance in correctly classifying effusions for further management.