Thymoma is the most common tumor of the anterior-superior mediastinum, especially in middle-aged or older adults. Microscopically, thymomas can be differentiated from other tumors with which they can be confused by the finding of a mixed population of cells, including neoplastic thymic epithelial cells with numerous processes surrounding activated-appearing lymphocytes. Thymomas can be classified as benign or malignant, and the majority of those that are malignant appear cytologically benign and are locally invasive. Cytologically benign thymomas have been classified as being lymphocyte rich, epithelial cell rich, or spindle cell type. This classification has not been found to be prognostically useful. A new method classifies these tumors as being cortical, medullary, or mixed. This new classification appears to have prognostic significance. Malignant thymomas that are cytologically malignant are uncommon. Such tumors usually are squamous cell carcinomas. Other types include sarcomatoid carcinoma, clear cell carcinoma, basaloid carcinoma, and mucoepidermoid carcinoma. Because other tumors can occur in the anterior mediastinum, electron microscopy and/or immunocytochemistry is helpful in making the distinction. The differential features by ultrastructural and immunocytochemical analysis are reviewed.