The results of application of transmission electron microscopy to the differential diagnosis of malignant tumors in needle aspirates are summarized. The analysis is based on the personal experience of the authors with 117 cases and the review of 223 cases published in the literature. The following four topics are discussed in detail: 1. Preparation of aspirates for transmission electron microscopic examination-limitations and advantages of various technical approaches. 2. Ultrastructural characteristics of malignant cells aspirated from various types of human tumors. 3. The diagnostic significance of ultrastructural examination of tumor cells in aspirates. 4. Transmission electron microscopy as compared to immunocytochemistry and to other methods used to aid differential diagnosis of needle aspirates. It is concluded that transmission electron microscopy when properly introduced into the diagnostic process helps to resolve many difficult problems of differential diagnosis of tumors in needle aspirates.