Two cases of malignant thymic neoplasms diagnosed by transthoracic fine-needle aspiration (FNA) biopsy under fluoroscopic and computerized axial tomography (CT) guidance with histologic, immunocytochemical, and ultrastructural confirmation are presented. The clinical and cytomorphologic features of the first case were typical of a malignant thymoma. A characteristic biphasic cell population of benign epithelial cells and mature lymphocytes was seen in Diff-Quik- and Papanicolaou-stained smears from the anterior mediastinal mass and the paravertebral metastasis and was confirmed by histologic examination. Immunoperoxidase studies for T and B cell subsets demonstrated lymphocytes with the thymic lymphocyte phenotype (Leu 6). Electron microscopic (EM) examination revealed epithelial cells with desmosomal attachments, tonofilaments, and extended cell processes along with mature lymphocytes. FNA biopsy of the second case demonstrated features of a thymic carcinoma. Individually scattered and loosely clustered small groups of markedly anaplastic and pleomorphic large cells were seen both in the Diff-Quik- and Papanicolaou-stained smears. EM performed on the FNA specimen demonstrated the poorly differentiated epithelial nature of the malignancy. The mediastinal mass was partially resected and demonstrated an undifferentiated carcinoma staining positively for low-molecular-weight cytokeratin. Ultrastructure demonstrated cell attachments and relationships consistent with carcinoma. The lack of a lung or other extrapulmonary primary tumor was consistent with a thymic carcinoma. These cases demonstrate the value of performing EM and immunocytochemistry on material obtained by fine-needle aspiration, which can aid in establishing the correct diagnosis and facilitate the clinical management of patients with malignant thymic neoplasms.