The presence of pleural tissue in transbronchial biopsies (TBs) is an incidental finding that has been rarely reported in the literature. It has the potential for causing wrong histologic diagnoses. Clinically, the significance of unintended pleural sampling by bronchoscopy is unknown. TBs containing mesothelial cells from 6 adult patients were studied using immunohistochemical stains. Clinical information was obtained with emphasis on the immediate postbronchoscopy period. The TBs were performed by 6 different bronchoscopists at 4 institutions because of pulmonary infiltrates in 5 patients and a mass lesion in 1 patient. All samples contained lung parenchyma and bronchial wall. They showed clusters of medium to large size polygonal cells with pink to amphophilic dense cytoplasm, round to oval nuclei, and prominent nucleoli. Some of the cells lined stroma and others were detached forming ribbons. They were initially disregarded, interpreted as carcinoma, judged as mesothelial cells, or interpreted as drug-induced reactive epithelial cells. They were positive for cytokeratin and showed nuclear staining for calretinin. They were negative for TTF-1, S100, CEA, and CD68. However, in 1 case, CD-68 positive histiocytes were admixed with enlarged reactive mesothelial cells corresponding to the so-called nodular histiocytic mesothelial hyperplasia. Chest x-ray films performed the same day after bronchoscopy showed no pneumothorax. Incidental sampling of the pleura may occur during the performance of TB and mesothelial cells may mimic carcinoma, pneumocytes, or macrophages. It is important to be aware of the presence of mesothelial cells in clinically uncomplicated TB to avoid an erroneous diagnosis of malignancy.