In this study, we investigated the regulation of TBX15 expression in human cancer cells, by analyzing the regulatory function of a 5’-distal conserved region of TBX15. Bisulfite sequencing showed high methylation of the CpG island contained in this region that was not correlated with TBX15 mRNA levels, in the cancer cell lines analyzed; however, after 5-aza-dC treatment of TPC-1 cells an increase of TBX15 expression was observed. This evidence concerns the gene TBX15 and cancer.