ARID1A is located in 1p36.11, a region frequently deleted in human cancers. Using a novel method to screen for tumorigenic cDNA sequences, we have identified ARID1A as a presumptive tumor suppressor gene. The transforming ARID1A sequence was an antisense cDNA, and was the product of a genomic rearrangement, as corroborated in the primary breast carcinoma from which the cDNA had been obtained. In further screening, we identified a lung adenocarcinoma cell line with a highly localized homozygous genomic deletion involving the 5′ end of ARID1A. These studies provide strong evidence that ARID1A is a tumor suppressor gene. © 2007 Wiley-Liss, Inc.