PURPOSE: SUMO-1 (small ubiquitin-related modifier-1) is a novel ubiquitin-like protein that is conjugated like ubiquitin, by a set of enzymes to cellular regulatory proteins including oncogenes and tumor suppressor genes. In this study, we aimed to investigate the significance of SUMO-1 expressions in cancerous esophageal lesions as a prognostic factor. METHOD: Tissue samples from 101 patients with esophageal squamous cell carcinoma were stained with anti-SUMO-1 antibody for immunohistochemical analysis. Using oligonucleotide microarrays, we analysed total RNA expression levels of ubiquitin-related genes in paired cancerous and normal tissue operative specimens in 12 patients. Immunoblot analysis of the paired cancerous and normal tissue samples were examined using an anti-SUMO-1 antibody. RESULT: SUMO-1 overexpression in cancerous tissues was related to lymphatic vessel invasion (p<0.001). Hierarchical clustering analysis using gene expression ratios (cancer/normal) divided the 12 patients into two groups. The expression of SUMO-1 was up-regulated in the poor prognostic cluster. Various bands of proteins conjugated with SUMO-1 were present in both cancerous and normal tissues. In esophageal squamous cell carcinoma, some peculiar bands which were absent in the normal tissue were recognized. CONCLUSION: In esophageal squamous cell carcinoma, overexpression of SUMO-1 correlated with lymphatic vessel invasion and a poor prognosis. SUMO-1 conjugation may important in the course of tumorigenesis.