I hypothesize that in the tumor process, LIF/LIFr might be at the basis of: (a) implantation of the primary tumor (CSC1s) via gp130-JAK-STAT3-ID1, with self-renewal and pluripotency (Niola et al., 2012); (b) subsequent paracrine growth (CSC1s/CSC2s) via gp130-JAK-STAT3-RAS-MAPK-ERK-MYC-WNT-ID2 (Cheng et al., 2001; Park et al., 2003); (c) genesis of cells with a mesenchymal phenotype (CSC3s) via CD44-STAT3-RAS-SNAIL1-MMPs-ID3-TWIST1 (Bain et al., 2001; Cheng et al., 2006; Su et al., 2011; Zeilstra et al., 2014; Yan et al., 2015). The gene discussed is CD44; the disease is neoplasm.