OBJECTIVE: To examine the performance of liquid-based cytology (LBC) on body cavity fluids as compared with conventional cytopreparatory techniques. STUDY DESIGN: Slides from a total of 592 serous fluids, effusions as well as intraoperative washings, were reviewed. Of these fluids, 301 were collected before and 291 after the introduction of the PrepStain LBC (TriPath Imaging, Burlington, North Carolina, U.S.A.) in our laboratory. RESULTS: PrepStain thin layers showed excellent morphology on a clear background, with preservation of 3-dimensional configurations and a sufficient amount of extracellular material to allow an accurate diagnosis. Cytopreparation, screening and interpretation of LBC were less time consuming. Moreover, when the performance of the various cytopreparatory techniques in malignant fluids was studied, PrepStain thin layers excelled over conventional cytopreparatory methods in showing a significantly lower false negative rate (P=.0414). CONCLUSION: Our findings indicate that in body fluid cytology, thin layers can safely replace other types of wet-fixed preparations, resulting in enhanced specimen quality and diminished false negative rates.