Recent studies have shown that microsatellite instability (MSI) may play an important role in the development of various types of cancer. However, there have been only 2 reports describing MSI in esophageal carcinoma and the clinicopathologic significance of MSI in this malignancy has not yet been clarified. To better elucidate the role of genetic instability in the development of esophageal carcinoma, we investigated the presence of MSI in 32 cases of esophageal cancer using paired samples of fresh frozen tumor and normal tissue by a method based on the polymerase chain reaction. MSI was defined as occurring in tumors which showed altered banding patterns at one or more microsatellite loci. The incidence of MSI in esophageal carcinoma was 6 out of 32 patients. MSI was observed more frequently in cases with small-cell carcinoma (2 out of 2) than in cases with squamous-cell carcinoma (4 out of 29). No cases with adenocarcinoma or Barrett's metaplasia were included in our series. No significant correlations between MSI and other clinicopathologic parameters were observed. The present study suggests that (1) some Japanese esophageal carcinomas certainly correlate with DNA replication error, and (2) MSI may be more frequent in small-cell carcinoma of the esophagus than in squamous-cell carcinoma of the esophagus.