Malignant pleural mesothelioma (MPM) is a rare cancer that metastasizes to mediastinal lymph nodes (MLNs). The diagnosis of MPM metastatic to MLNs may not be straightforward. We describe 3 cases to highlight unusual entities of MPM metastatic to MLNs as follows. One patient with a history of T3N1M0, poorly differentiated esophageal adenocarcinoma and malignant melanoma presented with shortness of breath, mediastinal lymphadenopathy, and pleural effusion; metastatic disease was clinically suspected. Unexpectedly, immunohistochemical studies supported the diagnosis of MPM metastatic to the MLN on biopsy. In another case, mesothelial cell inclusions were initially diagnosed based on the light microscopy, immunohistochemistry, and lack of pleural thickening on computed tomography studies. Subsequent fine needle aspiration of an enlarged cervical lymph node found an atypical mesothelial proliferation, and metastatic mesothelioma was strongly suspected. Video-assisted thoracoscopic examination showed small visceral nodules, and pleural biopsy was diagnosed as malignant epithelioid mesothelioma. The mediastinal and cervical lymph node biopsies were reinterpreted as positive for MPM. In the last case, MLN biopsy showed a malignant epithelioid cell proliferation. Calretinin, CK5/6, WT-1, D2-40, p63, and CD5 were immunohistochemically detected in the tumor but epithelial markers and TTF-1 were negative. Metastatic mesothelioma was considered based on immunohistochemistry and computerized tomography finding of pleural thickening even though p63 and CD5 positivity were unusual. In summary, MPM may present as mediastinal lymphadenopathy with metastases or it may be a concurrent neoplasm with other malignancies or shows an unusual immunohistochemical staining pattern. Caution should be used when diagnosing mesothelial cell inclusions in MLNs.