Background:Pleural effusion is a common finding in many malignancies.The present study was undertaken to determine the feasibility of cell block immunohistochemistry in cases presented with pleural effusion and finding the accuracy of the same in diagnosing the primary and finding the subtype. Methods:In this study, out of 200 cases of malignant pleural fluid effusion, 72 cases with no primary diagnosis were taken up. Based on the cytomorphology of conventional smears and cytoblocks cytomorphological diagnosis was offered. An immunopanel CK7, CK5/6, p63, TTF1, calretinin was applied on cell blocks. Additional immunochemical markers were performed based on clinical details and cytomorphology, wherever indicated. Results: The mean age of the patients was 50.8 years. The male to female ratio was 3.2:1. Cytomorphology was evaluated in all the 72 cases and IHC was used in 59 cases. After IHC 76.27% cases were confirmed as metastasis from lung primary, 10.1% from ovary, 3.3% from stomach and 10.16% from lymphoma. Other cases include mesothelioma(n=2), small cell carcinoma(n=2). Conclusion: Judicious use of IHC on cytoblocks of pleural fluid is effective in detection of lung carcinoma and its typing and also for detecting primary site in tumors of extrapulmonary origin especially in cases where obtaining a biopsy is technically challenging.