Histamine H1 receptor (H1R) belongs to the family of G protein-coupled receptors and is known to be involved in triggering cell proliferation and tumor growth besides its role in allergy and inflammation. In colorectal cancer, the lower survival rate in the patient group with high H1R expression levels was shown. On the other hand, the H1R expression levels at both mRNA and protein are reported to decrease in that disease. Therefore, the detailed relationship between H1R and tumor growth of colorectal cancer has not yet been elucidated. In this study, using HEK cells transiently transfected human H1R, we analyzed H1R functions in order to investigate the roles of H1R in colorectal cancer. The functional expression of H1R was confirmed by ligand binding, histamine-induced intracellular Ca²⁺ response and phosphorylation of extracellular signal-regulated kinase. Moreover, it was revealed that histamine-stimulation-independent cell permeability and migration ability were significantly increased in H1R-transfected HEK cells. These results suggest that H1R may contribute to the colorectal cancer metastasis through the histamine-independent constitutive activation of the receptor.