In the past molecular biological techniques have provided the basis for principally new aspects in the diagnosis of neoplastic diseases. The genetic predisposition to hereditary cancer syndromes can be detected by germ line DNA sequence analysis and offers the opportunity for prophylactic surgery. Some preneoplastic lesions can be detected through the identification of specific molecular alterations in nucleic acid preparations derived from various clinical samples. Residual or disseminated tumor cells can be detected in resection margins, lymph nodes, bone marrow, or peripheral blood with great sensitivity. Most likely, these techniques will strongly influence cancer screening programs and provide a rational basis for adjuvant systemic or regional therapy modalities. However, the clinical value of these techniques has not yet been proven in controlled trials. The problems of reproducibility and quality assurance have to be addressed and solved. This review summarizes the basic principles of some of these new molecular diagnostic techniques to permit a critical assessment of their clinical implications.