Malignant effusions, pleural effusion or ascites, represent a common problem in cancer patients. Pleural effusion in a cancer patient may be caused also by non-neoplastic conditions, and the diagnosis of malignant pleural effusion is established by the demonstration of tumor cells in pleural fluid. Microscopical detection of tumor cells in pleural fluid often fails, and there is an unmet medical need for more sensitive methods. New approaches, including isolation using magnetic beads coated with monoclonal antibodies targeting antigens expressed on tumor cells not only increase the diagnostic sensitivity, but also provide material for the analysis of predictive biomarkers. The advent of new technologies illustrates the incremental role of laboratory medicine in the management of patients with malignant effusions.