Molecular technology is being utilized increasingly for diagnostic purposes by practicing pathologists. Techniques such as Southern blot, in situ hybridization, and polymerase chain reaction have recently been introduced to the clinical laboratory setting. We describe a case of nasopharyngeal carcinoma that highlights the potential utility of DNA technology to secure an accurate diagnosis of a fine-needle aspiration biopsy. In this patient, cytologic examination of a cervical lymph node aspirate strongly suggested the possibility of a nasopharyngeal carcinoma. Needle aspirate material was submitted for molecular genetic detection of the Epstein-Barr virus (EBV) genome. Nine micrograms of DNA were isolated, and the presence of clonal EBV DNA was detected by the Southern blot technique. The presence of clonal EBV supported the cytologic diagnosis of nasopharyngeal carcinoma. Subsequent biopsy of a nasopharyngeal mass revealed undifferentiated carcinoma, and in situ hybridization revealed that EBV was restricted to the malignant epithelial cells. This case illustrates how molecular technology can provide new information that is useful in diagnostic cytopathology.