One of the major diagnostic challenges in routine surgical pathology is the group of spindle cell tumors. An extensive list of differential diagnoses is often relevant, and the need for an accurate diagnosis for treatment of the patients is evident. Although immunohistochemistry is a routine adjunct tool in most pathological laboratories, and molecular techniques are rapidly integrated, identification of ultrastructural features is still of great importance. For some tumor diagnoses, electron microscopy is more straightforward and timesaving than use of other methods, such as immunohistochemistry and molecular analyses. However, spindle cell lesions often require the use of all special techniques available. In this article, we discuss the role of electron microscopy in diagnosis of spindle cell tumors and focus upon some more recently described entities.