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1alpha,25-dihydroxyvitamin D3, the most active vitamin D derivative, is synthesized in the kidney, several epithelia and diverse cell types of the immune system. 1alpha,25-dihydroxyvitamin D3 is a pleiotropic hormone that, in addition to regulate calcium and phosphate metabolism and bone biology, inhibits cell proliferation and invasion, sensitizes to apoptosis and reduces angiogenesis and metastasis. Our group investigates 1alpha,25-dihydroxyvitamin D3 action in colon cancer: the effects on the phenotype of colon carcinoma cells by identifiying and studying its target genes, the antagonism of the Wnt beta-catenin/canonical and non-canonical signalling pathways, and the interaction with factors such SNAIL1/2 and ZEB1/2 that induce epithelial-to-mesenchymal transition. Recently, we have initiated the study of the action of 1alpha,25-dihydroxyvitamin D3 on human colon normal and cancer stem cells and on stromal fibroblasts isolated from healthy and tumoral biopsies from colorectal cancer patients.