Serous effusions occur as a manifestation of a variety of different diseases of a benign and malignant nature. Cytological diagnosis of serous effusions is based upon the distinction between benign and malignant cells at the light microscope level. This differentiation is not easy to perform in all cases due to the fact that benign reactive mesothelial cells may resemble the cells derived from adenocarcinoma or mesotheliomas. Aim of the study: This study is an attempt to improve the diagnostic accuracy of the cytological diagnosis of malignant effusions by investigating cjrtqlogic, immunocytochemical, and cytogenetic changes in cells exfoliated in those effusions. Patients and method: During the period from the first of August 2002 to the end of June 2004, (50) inpatients with effusions (pleural & ascitic), and having a high risk of malignancy, seen at Al-Kadhimya Teaching Hospital and The Hospital of Surgical Specialties in the Medical City, were included in this study. Effusion fluids were aspirated. All of the 50 specimens obtained were processed and examined by conventional cytologic technique and immunocytochemical technique using 2 monoclonal antibodies (p53 & CEA). In addition 15 selected specimens were studied by cytogenetic technique. All of the cases were followed up and the final clinical diagnoses were recorded that included various other investigations done including histopathology & the final clinical diagnoses were recorded that included various other investigations done including histopathology & the final clinician's opinion. The final clinical diagnosis was regarded then as the gold standard for comparative statistical work of this study. Results; The final clinical diagnosis revealed that 36 (72%) cases were malignant and 14 (28%) were benign. The sensitivity of cytology was 86.1%; specificity was 92.85%, with an overall accuracy of 88%. While the sensitivity, specificity, and accuracy of p53 were (63.8%, 92.8%, 72%) and of CEA were (72.22%, 85.7%, 76%) respectively. Combined p53 & CEA results showed a sensitivity of 83.33%, specificity of 85.71%, and an accuracy of 84%. And when both cytology and immunocytochemistry were combined in parallel the sensitivity was 91.66%, specificity was 85.7%, and the accuracy was 90%. The sensitivity of the cytogenetic technique, used for the 15 selected cases, was 70%, specificity was 100%, and the accuracy was 75%. It is concluded that using 2 or more (panel) selected monoclonal es will surely enhance the accuracy of immunocytochemical ue for malignancy detection while combined cytology & ipttUnoeytochemistry have higher accuracy than each of them alone. Adenocarcinoma of lung followed by that of breast were the most frequent primary tumors metastasizing to the pleural cavity. While idenocarcinoma of the ovary and stomach were the most frequent primary tumors metastasizing to the peritoneal cavity. While ftdenocarcinoma of the ovary and stomach were the most frequent primary tumors metastasizing to the peritoneal cavity. Conclusion: It is concluded that using 2 or more (oanel selected monoclonal antibodies will surely enhance the accuracy of immunocytochemical technique for malignancy detection while combined cytology & immunocytochemistry have higher accuracy than each of them alone. Cytogenetic technique if done optimally will be a great reassuring evidence for the presence of abnormal cells in the effusion fluids examined. While depending only on immunocytochemistry or cytogenetic analysis to decide a given case is malignant is not easily possible and both techniques appeared to be a supportive measure to conventional cytology. This study represents the starting point of an investigation of serous effusions using a combination of different techniques (immunocytochemistry & cytogenetics) that appeared to be applicable to effusion fluid specimens