One hundred twenty-six effusion samples from 102 patients were examined by cytology and flow cytometry (FCM). Overall, there was an 84% correlation between cytologic and FCM results. Of the 36 malignant cases determined by cytologic examination, FCM revealed an aneuploid peak in 20 (56%). Image analysis (IA) performed on the malignant cytologic cases with a diploid flow pattern detected two additional aneuploid peaks. In addition, FCM indicated three aneuploid cases in which cytologic characteristics were initially interpreted as benign (false negative). Aneuploidy was therefore detected in 64% of the malignant effusion specimens by FCM and IA. Twenty-three of the total of 24 aneuploid cases detected by FCM were associated with malignancy (predictive value = 96%). The one nonmalignant case was that of hemorrhagic pancreatitis with infected pseudocyst. FCM is an excellent tool when moderate to large numbers of tumor cells are present, whereas use of IA is advantageous for specimens containing smaller numbers of malignant cells because these can be directly analyzed. When an aneuploid peak is present, a diagnosis of malignancy must be suspected, and, if the initial cytologic screen is negative, a critical review of the cytology slides is justified. In those cases with an equivocal atypical cytology report and an abnormal cytometric histogram, additional investigation is warranted. In some malignancies the tumor cells will be diploid (in this study 36%) and neither FCM nor IA will add to tumor detection, leaving cytologic examination as the definitive technique.