BACKGROUND:The International System for Reporting Serous Fluid Cytopathology (ISRSFC) was published recently to provide standard reporting terminology for serous fluid. To date, several ISRSFC reclassification studies have reported a wide range of diagnostic category frequency and the associated risk of malignancy (ROM). Herein, the authors applied the ISRSFC to report pleural and peritoneal effusions retrospectively in a community hospital setting. METHODS: With Internal Review Board approval, 446 peritoneal effusion specimens and 299 pleural fluid specimens from 576 patients in three community hospitals over a 12-month period were reviewed and reclassified according to the ISRSFC. RESULTS: After reclassification, in pleural effusions, 18 (5.0%) were nondiagnostic (ND), 273 (76.0%) were negative for malignancy (NFM), 18 (5.0%) were atypia of undetermined significance (AUS), 6 (1.7%) were suspicious for malignancy (SFM), and 44 (12.3%) were malignant (MAL). In peritoneal effusions, after reclassification, 11 (5.5%) were ND, 168 (77.1%) were NFM, 9 (4.1%) were AUS, 2 (0.9%) were SFM, and 27 (12.4%) were MAL. The calculated ROM was 0.0% for ND, 1.8% for NFM, 37.5% for AUS, 83.3% for SFM, and 100.0% for MAL in peritoneal effusions; and the ROM was 8.3% for ND, 1.2% for NFM, 44.4% for AUS, and 100.0% for both SFM and MAL in pleural effusions. Further analysis demonstrated notable heterogeneity among published ISRSFC reclassification studies, although the overall ROMs did not differ significantly from the ISRSFC-determined ROMs (all p values were > .05 for mean ROM comparisons). CONCLUSIONS: The findings suggested the necessity for each laboratory to perform its own ROM analysis based on its statistics for ISRSFC-tiered classification terminology.