Building on previous reports that NHE1 activity and expression is increased in human cancers (McLean et al., 2000; Miraglia et al., 2005; Chiang et al., 2008; Yang et al., 2011), we show that engineered over-expression of an NHE1 ortholog in vivo increased pHi by ∼0.3 pH units, which is comparable to the increase seen with oncogene transformation. This evidence concerns the gene SLC9A1 and cancer.