We describe a patient with hyperplastic mesothelial cells localized to mediastinal lymph node sinuses. These mesothelial cells were originally misdiagnosed as metastatic carcinoma, and the patient received radiotherapy. Histologic review, immunohistochemistry, and ultrastructural studies confirmed mesothelial cell origin. These nodal mesothelial cells were associated with pericardial and pleural effusions. Extranodal lymphatics also contained hyperplastic mesothelial cells, confirming their mode of lymphatic transport to node sinuses. This finding supports the theory that hyperplastic mesothelial cells derive from reactive serosal mesothelium and are dislodged into draining lymphatics. This is the first report, to our knowledge, that demonstrates the pathogenetic significance of this lymphatic transport mechanism. Awareness of intralymphatic and nodal benign hyperplastic mesothelial cells and their mimicry of invasive malignant neoplasms is important for accurate diagnoses and appropriate therapy.