Abstract: The P16 gene mapped on the short arm of chromosome 9(9p 21 ) was found to delete or mutate in various primary tumors and in a large number of transformed cell lines.To study the involvement of the p16 tumor suppressor gene in primary esophageal squamous cell carcinomas,we used the PCR-SSCP method to examine mutation frequency of the P16 gene exon2 in 22 primary esophageal squamous cell carcinomas and their corresponding normal tissues.Mutation of the P16 gene exon2 was observed in 9 out of 22 primary esophageal squamous carcinomas.There was no mutation in the normal tissues.The mutation rate of the P16 gene exon2 was higher in poorly differenciated squamous cell carcinomas than in well differenciated cancers ( P =0 038).The same result was observed between clinical stage Ⅳ and clinical stage Ⅱ、Ⅲ( P =0 042).It is suggested that mutation of the P16 gene exon2 is involved in most primary esophageal squamous cell carcinomas and that P16 gene mutation plays a critical role in the esophageal tumorigenesis.