A retrospective review of 189 fine-needle aspiration (FNA) biopsies of the mediastinum from four university medical centers was performed. Review of Diff-Quick- and Papanicolaou-stained direct smears was performed from a series of 189 FNA biopsies along with surgical pathology correlation obtained in 42% of the cases. There were 28 (14.8%) nondiagnostic or unsatisfactory for diagnosis cases. Of the satisfactory FNA specimens with histologic correlation, 12 cases (6%) were discordant. These errors primarily involve subclassification of small-cell malignancies involving the mediastinum, including a misdiagnosis of small-cell carcinoma for lymphoma. Large-cell lesions that were problematic included the accurate diagnosis of Hodgkin's lymphoma including the separation from non-Hodgkin's lymphoma. Large-cell lymphoma with sclerosis was misinterpreted in two cases due to distortion of cells by the mesenchymal tissue and sparsely cellular smears. In two cases classification of primary germ-cell tumors and separation from metastatic carcinoma was a problem. In general, FNA of the mediastinum is an accurate procedure, but can be challenging in a minority of cases due to sparse cellularity of the lesions and accurate classification of a variety of neoplasms that occur in this region. These 12 discordant cases serve as the basis of our report.