Ion channels have been implicated in both the behaviours of cancer cells and the development of cancer. Potassium channels (KCh) play fundamental roles in cell behaviours linked to cancer progression, including proliferation, migration and apoptosis. One family, the two-pore domain (K2P) KCh are of particular interest since when functionally expressed these channels are constitutively active. Of the 15 K2P family members, 4 channels; K2P2.1, K2P3.1, K2P9.1, K2P5.1, are reported to show expression and functional implications in cancer. Supporting the hypothesis that alterations to K2P channels expression or function may play a role in cancer progression and that targeting these channels may lead to novel therapies. To determine the expression of the KCNK genes, encoding the K2P channels, in a range of cancer types we used the online cancer microarray database, Oncomine (www.oncomine.org). Each gene was examined across 20 cancer types, comparing mRNA expression in cancer to normal tissue. Searches were performed using threshold criteria (p-value < 0.05, fold change > 2, gene rank percentile < 10%) so that positive analyses for altered expression were above these. mRNA expression of K2P channels were also examined in human cancer cell lines by RT-PCR. Significantly overexpression of K2P channels was observed in a range of cancers including breast, leukaemia and lung. The data highlights K2P channels with overexpression in a range of cancers; K2P1.1, K2P3.1, K2P12.1. More cancers and channels showed underexpression rather than overexpression, suggesting that underexpression of K2P channels may be important in cancer. Six K2P channels have a wide underexpression pattern across the cancer types examined; K2P1.1, K2P3.1, K2P5.1, K2P6.1, K2P7.1, K2P10.1. There was significant underexpression of K2P channels in a wide range of cancer types; brain, colorectal, gastrointestinal, kidney, lung, melanoma, oesophageal. Three K2P family members; K2P4.1, K2P16.1, K2P18.1 did not show altered expression in cancer. Using RT-PCR we examined the expression of K2P3.1 mRNA in cancer cell lines and found expression in breast, lung and kidney cell lines. K2P9.1 mRNA was also identified in several cancer cell lines including brain, breast, colorectal, and oesophageal. K2P15.1 mRNA has been detected in all cancer cell lines examined to date. K2P channels alter cell resting membrane potential therefore altered expression in cancer cells would change this potential and influence the activity of other ion channels causing behavioural consequences. K2P channels also show sensitivity to physiological stimuli including pH, oxygen tension and glucose concentration; physiological parameters which are disrupted in the tumour microenvironment. This information will be instrumental towards understanding the role of K2P channels in cancer progression.