Histidine decarboxylase (Hdc) is required for the endogenous production of histamine, but its role in tumorigenesis is unclear. Yang et al. now report that Hdc-deficient mice develop more tumors in models of chemically induced carcinogenesis, associated with an increased recruitment of immature myeloid cells to the tumors and higher amounts of interleukin-6. The authors further show that Hdc deficiency inhibits myeloid cell maturation and that exogenous histamine promotes monocyte differentiation and suppresses tumor growth.