An effective way to decrease the mortality rate in esophageal cancer (EC) is to provide diagnosis and treatment for early EC patients. Identification of molecular markers would be helpful for early diagnosis. In this study, we obtained the gene expression profile of early esophageal squamous cell carcinoma (ESCC) and further screened molecular markers that might be useful in early diagnosis and treatment. RNA extracted from EC cancer tissues and matched normal esophageal epithelium of four EC patients were analyzed using whole-genome microarrays. Welch's t-test was applied to normalized data to identify genes expressed differently between cancer and normal tissues. Significantly differentially expressed genes were classified according to gene ontology. Gene mapping software was used to identify pathways involving the genes that were significantly changed. Among the 54,613 gene transcripts and variants analyzed, 367 were differentially expressed between early ESCC and normal esophageal epithelium (Welch's t-test, P<0.01). Specifically, 104 genes were significantly upregulated and 263 were downregulated in early ESCC, compared with normal esophageal epithelium. Functional gene sets expressed differentially between ESCC cancer and normal tissues included those involved in gene transcription, cell proliferation, motility, apoptosis, and metabolism (specifically, pathways of cell apoptosis, the cell cycle, G protein, and TGF-beta signal transduction). We conclude that a large number of genes are involved in the occurrence and development of early ESCC and take part in various cell processes and pathways. The present findings contribute theoretical information for further screening of genes related to early ESCC.