The human nm23 gene, a candidate metastatic suppressor gene, consists of two genes, nm23-H1 and nm23-H2. The potential mutation in the nm23-H1 gene was examined in colorectal cancer using a reverse transcription polymerase chain reaction amplification followed by DNA sequencing analysis. Genomic alterations in the nm23 gene were also examined by Southern hybridization. Genetic alterations either as a deletion in the coding sequence of nm23-H1 or as an allelic deletion were detected in four among eight colorectal adenocarcinomas associated with metastases in lymph nodes, lung, or liver. No alteration was observed in 12 additional colorectal cancer specimens without metastasis. These results provide first evidence for novel mutation in the nm23 gene and demonstrate a correlation between the mutation in the nm23 gene and metastasis in colorectal oncogenesis which suggests that the nm23 gene plays a role in the causation of metastasis.