The majority of human colorectal cancers have elevated β-catenin/TCF regulated transcription due to either inactivating mutations of the APC tumor suppressor gene or activating mutations of β-catenin. Surprisingly, one commonly used colorectal cancer cell line was found to have intact APC and β-catenin and no demonstrable β-catenin/TCF regulated transcription. However, this line did possess a truncating mutation in one allele of CDX2, a gene whose inactivation has recently been shown to cause colon tumorigenesis in mice. Expression of CDX2 was found to be induced by restoring expression of wild type APC in a colorectal cancer cell line. These findings raise the intriguing possibility that CDX2 contributes to APC's tumor suppressive effects.