Numerous reviews of adenocarcinoma arising in Barrett's esophagus have been reported, but detailed pathologic findings or survival analysis have rarely been provided. This retrospective study analyzed 67 patients (mean age, 64 years; male-to-female ratio, 10:1) with an adenocarcinoma arising in Barrett's esophagus treated by surgical resection. Prevalence of smokers was 63%, alcohol users, 45%, and patients with hiatal hernia, 73%. Five patients had another synchronous cancer, and seven patients, previous esophageal surgery. Forty percent of the tumors were well differentiated, 31% moderately differentiated, 15% poorly differentiated, 7% mucinous, and 6% composed of signet-ring cells. Depth of invasion in the esophageal wall was limited to mucosa in 13% of cases and submucosa in 18%. Invasive adenocarcinomas extended to the muscular layer in 12% of cases, to adventitia in 33%, and to periesophageal tissue in 24%. Vascular and perineural neoplastic invasion was present in 67 and 38% of cases. Regional lymph node involvement and distant metastases were found in 51 and 9% of cases. Overall, 1-, 2-, and 5-year survival rates were 63, 41, and 32%, respectively. Five-year survival rate was significantly better for patients with superficial cancer limited to mucosa or submucosa (82 vs. 12%) or without regional lymph node involvement (59 vs. 10%). Tumor differentiation, vascular and perineural invasion, extranodal spread, distant metastases, and resection margins status also had a significant prognostic value on univariate analysis. In a multivariate Cox regression analysis for overall survival, depth of invasion in the esophageal wall and regional lymph node involvement were independent prognostic factors. Careful pathologic staging is of value in determining the prognosis of patients with adenocarcinoma arising in Barrett's esophagus.