Colorectal cancers are a major cause of death; many start as adenomas, growing and becoming dysplastic, with an increasing risk of malignant change. Dysplastic transformation is associated with depolarisation of the crypt epithelia cells, possibly indicating a change in K channel regulation or expression. Three K channel species have previously been identified in human colonic crypt cells by functional and RT-PCR studies: KCNQ1/KCNE3, KCNN4 and KCNMA1 (Sandle et al. 1994; Morton et al. 2001). Using real-time quantitative PCR (Lightcycler, Roche), the mRNA expression of K channels was measured in human colonic cancer and macroscopically normal adjacent tissue. Tissue was obtained, with consent and local ethical committee approval, from patients undergoing tumour resection. Tissues were embedded in optimum cutting temperature (OCT) medium, snap-frozen and sliced on a cryostat. RNA was isolated using the TRIzol method with 1μg total RNA added to the reverse transcription reaction. K channel mRNA expression was determined using the delta CP method (Pfaffl, 2001) and normalised to β-actin and 28-S RNA levels. Expression of the basolateral small conductance K channel encoded by KCNQ1 and its associated β subunit KCNE3, were both significantly elevated in the cancer by 2.6 ± 0.5 and 2.5 ± 0.5-fold, respectively (mean ± SEM), (p<0.05, n = 8). Similarly the basolateral intermediate conductance K channel (KCNN4) was increased by 3.0 ± 1.3-fold in the cancer tissue (p0.05, n = 8). Statistics were performed on log transformed data using a 1-tailed t test. This study shows that the mRNA expression of KCNN4 and KCNQ1/KCNE3 is increased in colon cancer, whereas KCNMA1 appears unchanged. If the changes in K channel expression observed in colon cancer are mirrored in adenomatous polyps, then these channels may provide a biomarker for malignant potential.