The authors assessed the relationship between dysplasia in Barrett's esophagus and invasive adenocarcinoma in a study of both endoscopic biopsy specimens and esophagectomy specimens. They reviewed the pathologic findings and clinical follow-up of 14 patients with dysplasia in Barrett's mucosa in endoscopic biopsy specimens. They also studied systematically the histopathologic features of the Barrett's mucosa in 43 esophagectomy specimens resected for Barrett's carcinoma. In the biopsy specimens, dysplasia occurred in distinctive-type Barrett's mucosa of 13 patients (93%) but in cardiac-type mucosa of only 3 (21%). Six patients had high-grade dysplasia; five underwent esophagectomy and three of these were found to have superficially invasive adenocarcinoma. The other patient with high-grade dysplasia as well as eight patients with intermediate- or low-grade dysplasia are not known to have carcinoma on available follow-up. In the study of resection specimens, high-grade dysplasia was strongly associated with adjoining invasive adenocarcinoma, because 84% of areas with invasion had high-grade dysplasia and 92% of areas with high-grade dysplasia showed invasion. The authors' findings suggest that the dysplasia-carcinoma sequence most commonly occurs in Barrett's mucosa of the distinctive type; high-grade dysplasia in Barrett's mucosa is a marker indicating high probability of invasive carcinoma; the presence of high-grade dysplasia in biopsy specimens of Barrett's mucosa is an indication for esophagectomy in suitable surgical candidates.