Tumor-associated macrophages (TAMs) encourage and coordinate neoplastic growth. In late stage human lung adenocarcinoma, TAMs exhibited mixed M1 (classical; argI low iNOS high ) and M2 (alternative; argI high iNOS low ) polarization based on arginine metabolism. In several murine cancer models including chemically and genetically-induced primary lung tumors, prostate tumors, colon xenografts, and lung metastases, TAMs expressed argI high iNOS low early during tumor formation; argI low iNOS high polarization also occurred during malignancy in some models. In a chemically-induced lung tumor model, macrophages expressed argI high iNOS low within one week after carcinogen treatment, followed by similar polarization of bone marrow–derived monocytes (BDMCs) a few days later. TAMs surrounding murine prostate tumors also expressed argI high iNOS low early during tumorigenesis, indicating that this polarization is not unique to neoplastic lungs. In a human colon cancer xenograft model, the primary tumor was surrounded by argI high iNOS low -expressing TAMs, and BDMCs also expressed argI high iNOS low , but pulmonary macrophages adopted argI high iNOS low polarization only after tumors metastasized to the lungs. Persistence of tumors is required to maintain TAM polarization. Indeed, in both conditional mutant Kras- and FGF10-driven models of lung cancer, mice expressing the transgene develop lung tumors that regress rapidly when the transgene is silenced. Furthermore, pulmonary macrophages expressed argI high iNOS low on tumor induction, but then returned to argI low iNOS low (no polarization) after tumors regressed. Manipulating TAM function or depleting TAMs may provide novel therapeutic strategies for preventing and treating many types of cancer.