Background: Significantly lower LINE-1 methylation level has been observed in several cancers, compared to their normal cell counterparts. It is of interest to note that this epigenetic phenomenon is rather common to cancers with multistage oncogenesis. Objective: To compare LINE-1 methytlation level of cancer cells between the primary and matched metastatic sites. Methods: COBRA method was used to determine LINE-1 methylation level of tumor cells at the primary and matched metastatic sites in 5 malignancies (10 cases each of head and neck squamous carcinoma, papillary thyroid carcinoma, non-small cell lung cancer, invasive mammary ductal carcinoma, and colorectal adenocarcinoma). LINE-1 methylation level between the primary and matched metastatic site was compared. Results: In head and neck cancer and lung cancer, significantly lower LINE-1 methylation level was noted in the metastatic site, compared to the primary site (p < 0.01). Significant changes in direction of LINE-1 methylation in many loci were found in breast cancer (p < 0.05) but not in LINE-1 methylation levels. No significant changes in LINE-1 methylation level, between the primary and matched metastatic site, were found in the remaining cancers tested. Conclusion: Significantly lower LINE-1 methylation level was found at the metastatic site of head and neck cancer and lung cancer, as compared to the matched primary tumor. Further studies are warranted to determine whether this altered methylation is the result or the cause of cancer metastasis.