Evaluation of serous effusions can include immunocytochemical stains that differentiate reactive mesothelial cell from adenocarcinoma cell. Among several positive mesothelial cell markers, we used desmin, CK5/6, WT1 and calretinin all known to have high sensitivity and specificity as selective mesothelial cell markers. We studied smears obtained with cytospin from 15 malignant and eight benign effusions. The mesothelial cells were positively stained by desmin, CK5/6, WT1 and calretinin in 60.9%, 29.1%, 26.7% and 56.5%, respectively among 8 benign and 15 malignant effusions; the adenocarcinoma cells were positively stained 6.7%, 13.3%, 1.0% and 0.0%, respectively among 15 malignant effusions. The percentage of positively stained mesothelial cells were somewhat lower for all antibodies compared to the results of previous studies. This was likely due to the differences in preparation methods and fixatives among studies. In conclusion, the use of desmin and calretinin were more valuable than CK5/6 and WT1 for distinguishing between reactive mesothelial cell and adenocarcinoma cells in serous effusion; however, choice of the proper preparation methods and fixatives are also important