Background The International System for Reporting Serous Fluid Cytopathology was recently proposed as a tiered structure to provide consistent reporting terminology for serous effusions. Because of the variation in reporting practices for indeterminate serous effusions, namely, the atypia of undetermined significance (AUS) and suspicious for malignancy (SFM) groups, the authors retrospectively reviewed cases in these 2 categories at their institution and determined the associated risk of malignancy (ROM). Methods Pleural, peritoneal, and pericardial effusions that were reported as AUS or SFM over a 1‐year period were reviewed, and their associated ROMs were calculated based on confirmation of malignancy by previous and/or subsequent fluid and/or tissue biopsy specimens from the same general location. Results In total, 145 AUS and 98 SFM serous effusion cases were identified. The AUS category was used when the cells in question lacked the requisite quantitative (cell number) and/or qualitative (morphologic) features for a definitive diagnosis. Immunohistochemistry (IHC) or flow cytometry (FCM) was available in 15% of cases (n = 22) with inconclusive results. The ROM based on 69 cases with available follow‐up results was 39%. In contrast, the SFM category demonstrated cells that were morphologically suspicious for malignancy but sparse, precluding IHC or FCM (n = 63; 64%) or yielding inconclusive results (n = 35; 36%). The ROM in the SFM category, based on follow‐up results of 61 cases, was 64%. Conclusions The ROM for SFM was significantly higher than that for AUS (P < .01), supporting separate diagnostic categories for these 2 groups. There is considerable variation in the reporting practices for indeterminate serous effusions, namely, the categories atypia of undetermined significance and suspicious for malignancy, with limited literature on their associated risk of malignancy. The reporting practice at a single institution is examined and demonstrates that the risk of malignancy in the suspicious for malignancy category is significantly higher than that for the atypia of undetermined significance category, thus providing support for retaining these as 2 separate diagnostic categories in the tiered reporting system for serous effusions.