Tumor and matched normal tissue from 19 esophageal squamous cell carcinoma patients from a high-risk area of China were analyzed with 7680 gene cDNA microarrays. Forty-one genes were differentially expressed (P < 0.001; >/==" BORDER="0">2-fold change) between tumor and matched normal samples (13 overexpressed and 28 underexpressed). Hierarchical clustering showed consistent molecular profiles across patients. Multidimensional scaling plots visually distinguished cases by family history status, which was confirmed statistically using a global permutation test (P = 0.007); we then identified 152 genes of which the expression differed in tumors from family history positive versus negative cases (55 overexpressed and 97 underexpressed at P < 0.001). These data indicate that molecular profiles in esophageal squamous cell carcinoma are highly consistent and that expression patterns in familial cases differ from those in sporadic cases.