The degradation of the extracellular matrix (ECM) is a major step in the process of tumor invasion and metastasis, mediated by matrix metalloproteinases (MMPs). Knowledge of alterations in the expression of stromelysin-2 (ST-2) or MMP-10 in human esophageal squamous cell carcinoma (ESCC) is meager. Immunohistochemical analysis of ST-2 expression was carried out in surgically resected ESCCs (50 cases) and paired distal histologically normal esophageal tissues (50 cases), correlated with clinicopathological parameters. Overexpression of ST-2 protein, in tumor cell cytoplasm and stromal elements, was observed in 37 of the 50 (74%) ESCCs localized in tumor cell cytoplasm and stromal elements. Low levels of ST-2 were observed in 8 of the 50 (16%) matched histologically normal esophageal tissues. Significant associations were observed between ST-2 overexpression and tumor size (r = 0.02, P = 0.04), local invasiveness of the tumor (r = -0.30, P = 0.002) and distant organ metastasis (r = -0.227, P = 0.02), suggestive of its involvement in development and progression of ESCCs. The data underscore the significance of ST-2 expression in context to the aggressive tumor characteristics observed in ESCCs in the Indian population, wherein extremely poor prognosis has been ascribed to extensive local invasion and metastasis.