HB‐EGF secreted by tumor cells has been shown to suppress the expression of OPG in osteoblasts, which in turn promotes osteoclastogenesis and produces an environment for tumor cell metastasis.16 In contrast, another study shows that expression of a dominant negative EGFR mutant increases the expression of RANKL in osteoblasts, which in turn promotes osteoclastogenesis and leads to a decrease in bone mass.22 However, our Dermo1‐Cre‐mediated HB‐EGF knockout mice and Dermo1‐Cre‐mediated HB‐EGF overexpression mice showed no significant change in osteoclastogenesis or bone resorption. This evidence concerns the gene HBEGF and neoplasm.