The chromosome region 18q21 is frequently deleted in lung cancers. Recent identification of JV18-1 at this locus led us to examine whether or not it might also be altered in lung cancers, as is the case for the closely related DPC4 tumor suppressor gene. A missense somatic mutation and a 9-bp in-frame deletion were detected in the highly conserved region of JV18-1 among 57 lung cancer specimens taken directly from patients. The total alterations in JV18-1 and DPC4, however, are not sufficient to account for all 18q21 deletions in lung cancers. These findings suggest that although JV18-1 and DPC4 may play roles in a limited fraction of lung cancers, another tumor suppressor gene may also exist in this chromosome region.