Protocadherins are celladhesion molecules with 6 or 7 cadherin motifs in their extracellular domain and various cyotoplasmic domains. PCDH10 was characterized a novel tumor suppressive gene in and was epigenetically silenced in multiple haematologic malignancies as well as some solid tumors such as gastric cancer, nasopharyngeal carcinoma and esophageal carcinoma. High-resolution melting (HRM) analysis has been used as a novel tool for analysis of promoter methylation. In our study, we used HRM analysis to detect the methylation levels of PCDH10 gene in 100 gastric cancers, 100 colorectal cancers, 70 pancreatic cancers and equal number of adjacent normal tissues. The frequency of PCDH10 methylation in all three types of cancers was significantly higher than that in normal tissues. Consistent with previous reports, expression levels of PCDH10 were inversely correlated with methylation levels. But we didn't find significant association between PCDH10 methylation status and TNM staging in all three types of cancers. In summary, application of HRM analysis to large amount of clinical samples proves to be a fast and high-throughput way to investigate the epigenetic status of PCDH10. And this is the first study to evaluate the prevalence of PCDH10 methylation based on large amount of tumor samples, showing that epigenetic regulation of PCDH10 was associated with carcinogenesis.