Cyto-pathogical examination plays a vital role in the preliminary work up of the serous cavity effusion fluids to find out the possible aetiology weather benign or malignant. Amongst malignant effusions, cytology is helpful in determining the exact type, cellular morphology, site, and stage of the tumour. Serosal fluid samples are obtained for two purposes: one, for diagnostic purpose, by needle aspiration and second, for therapeutic purpose, by evacuation of symptomatic pleural, pericardial or peritoneal effusions to relieve dyspnea or discomfort. However, for reporting effusion cytology specimens, there is no consistent and reproducible effusion sample processing system developed. Aim: The intention of this chapter is to provide the basic and advanced technicalities for processing the serous fluid examination has been mentioned to initiate the uniformity in the sample processing in cyto-pathology laboratory. For effusion cytology a proper collection, transportation and preparation of cell samples are the prerequisites for a reliable cyto-pathological diagnosis.