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CD44 is an adhesion protein whose expression differs in normal and cancerous cells of various tissues. In comparison with most countries, the incidence rate of esophageal squamous cell carcinoma in Iran is quite high. Here, expression of the standard form of CD44 (CD44S) and forms containing variant exons V3, V6 and V7 were compared in normal and cancerous esophageal tissue of 42 (or more) Iranians afflicted with cancer of the esophagus. Expression was detected by immuno-histochemical techniques. Statistically significant differences between normal and cancerous cells were in the expression of V6 and V7 and CD44S. A larger percent of normal samples expressed V6 and V7 and the intensity of expression of CD44S was higher in the cancerous samples. The cellular location of expression of CD44S and all three variant exons was also distinctly different in the two types of samples. Additionally, within the cancerous samples it was noted that the percent of CD44S expressing samples increased with decreasing differentiation and of V7 expressing samples decreased with increasing invasiveness. Such differences suggest that CD44 expression is somehow related to the cancerous state of esophageal squamous cell carcinoma.