BACKGROUND Benign body cavity effusions sometimes cannot be distinguished from malignant ones by conventional cytology. The authors performed fluorescence in situ hybridization (FISH) on ThinPrep slides using chromosome specific probes to see if hyperdiploid malignant cells could be detected in 20 body cavity effusions. The results were then compared with those of conventional cytology. METHODS A total of 20 body cavity effusions from 19 patients were studied using conventional cytology and FISH. Probes specific for chromosomes 3, 8, 10, and 12 were used to detect hyperdiploidy on ThinPrep slides (Cytyc Corporation, Boxborough, MA). RESULTS A total of 13 patients had malignant conditions (either prior history of malignancy or the presence of malignancy anywhere in the body). Conventional cytology and FISH were both positive in 5 of these patients (6 samples) and negative in 2 patients. The results for one sample were inconclusive by both methods. There were 5 discrepant cytology‐FISH results in patients with malignant conditions. One sample was positive by FISH and negative by cytology, one was positive by FISH and “atypical” by cytology, and three were inconclusive by FISH and negative by cytology. FISH results were either negative (in 4 samples) or inconclusive (in 2 samples) in the 6 patients with benign conditions. CONCLUSIONS FISH can detect hyperdiploid malignant cells in body cavity effusions and is especially useful when the major cell population consists of malignant cells that cannot be differentiated from mesothelial or “atypical” cells. It is less useful in detecting a small population of malignant cells hidden in an inflammatory or reactive cell background. More studies are needed to establish diagnostic criteria further and to assess the clinical usefulness of this procedure. Cancer (Cancer Cytopathol) 1997; 81:299‐308. © 1997 American Cancer Society.