Samples of Barrett metaplastic specialized epithelium (SE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive adenocarcinoma (CA) derived from 36 esophagectomy specimens were studied for loss of heterozygosity (LOH) in APC and MCC and for expression of APC protein. Of 18 cases that were heterozygous (informative) for APC, LOH was found in none of 14 SE samples, 2 of 8 LGD samples, 3 of 11 HGD samples, and 5 of 17 CA samples. Immunohistochemically, markedly reduced expression of APC protein (< 50% positive cells) was found in 3 of 19 HGD samples and 4 of 35 CA samples but not in SE or LGD samples. Of 17 cases informative for the MCC gene, LOH was detectable in 1 of 14 SE samples, none of 7 LGD samples, none of 9 HGD samples, and 4 of 16 CA samples. Allelic loss of APC and/or loss of APC protein expression occurs earlier in the metaplasia-dysplasia-carcinoma sequence in Barrett esophagus than LOH in the MCC gene. The determination of alterations at APC or MCC would be of limited importance for the surveillance of patients with Barrett esophagus.