ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) is a family of proteins characterized by the presence of a metalloproteinase domain linked to a variety of specialized ancillary domains. The ADAMTS9 gene (ADAM metallopeptidase with thrombospondin type 1 motif, 9); has been characterized as a novel tumor suppressor gene in and epigenetically silenced in association with lymph node metastases in nasopharyngeal carcinoma. High-resolution melting (HRM) analysis has been used as a tool for analysis of promoter methylation. Here, we report HRM analysis used to detect the methylation levels of ADAMTS9 gene in 100 gastric cancers, 100 colorectal cancers, 70 pancreatic cancers, and an equal number of adjacent normal tissues. The frequency of ADAMTS9 methylation in all three types of cancers was significantly higher than in normal tissues. Consistent with previous reports, expression levels of ADAMTS9 were inversely correlated with methylation levels. There was no significant association between ADAMTS9 methylation status and tumor-node-metastasis staging in all three types of cancers. In summary, application of HRM analysis to large numbers of clinical samples is a rapid and high-throughput way to investigate the epigenetic status of ADAMTS9. The present study is novel in evaluating the prevalence of ADAMTS9 methylation based on a large number of tumor samples and showing that epigenetic regulation of ADAMTS9 was associated with carcinogenesis.