Some undifferentiated gastric carcinomas with intense lymphoid infiltration have a striking resemblance to nasopharyngeal lymphoepithelioma. The authors identified eight such cases (seven patients from Japan and one from the United States) of undifferentiated gastric carcinoma (lymphoepithelioma-like carcinoma [LELC]) and examined them for Epstein-Barr (EBV) viral sequences using polymerase chain reaction (PCR) and in situ hybridization (ISH) techniques. EBV was detected in seven of the eight cases by PCR, including a lymph-node metastasis. ISH that was performed in six of these cases showed EBV genomes to be uniformly present in the carcinoma cells and not present in the reactive lymphoid infiltrate or normal gastric mucosa. PCR of a polymorphic EBV locus (lymphocyte-determined membrane antigen) showed that a single genotype was present in each gastric LELC, consistent with a clonal process. These findings suggest that some undifferentiated gastric carcinomas are EBV-related and that focal EBV infection occurs before transformation.