The PTEN/MMAC1/TEP1 gene has been isolated as a tumor suppressor gene that is altered in several types of human tumors including brain, breast, and prostate cancers. In the present study, we report PTEN/MMAC1/TEP1 alterations in human lung cancers. Intragenic homozygous deletions were detected in 6 (40%) of 15 small cell lung carcinoma (SCLC) cell lines and in 2 (8%) of 25 non-small cell lung carcinoma (NSCLC) cell lines. A nonsense mutation and a missense mutation were detected in 2 (8%) NSCLC cell lines. An intragenic homozygous deletion, a 1-bp frameshift mutation, and a nonsense somatic mutation were also detected in three (6%) of 47 surgical specimens. All the lung tumors with PTEN/MMAC1/TEP1 mutations were homozygous for the mutant alleles. These findings suggest that PTEN/MMAC1/TEP1 plays a role as a tumor suppressor gene in the genesis and/or progression of human lung cancer.