The roles of tumor-associated macrophages (TAMs) and circulating monocytes in human cancer are poorly understood. Here, we show that monocyte subpopulation distribution and transcriptomes are significantly altered by the presence of endometrial and breast cancer. Furthermore, TAMs from endometrial and breast cancers are transcriptionally distinct from monocytes and their respective tissue-resident macrophages. We identified a breast TAM signature that is highly enriched in aggressive breast cancer subtypes and associated with shorter disease-specific survival. We also identified an auto-regulatory loop between TAMs and cancer cells driven by tumor necrosis factor alpha involving SIGLEC1 and CCL8, which is self-reinforcing through the production of CSF1. Together these data provide direct evidence that monocyte and macrophage transcriptional landscapes are perturbed by cancer, reflecting patient outcomes. Display omitted •Cancer alters circulating monocytic populations and their transcriptomes•Tumor-associated macrophages show tissue-specific programming•Tumor-associated macrophages’ gene signature correlates with poor clinical outcome•Tumor-associated macrophages enhance cancer cells malignancy through CCL8 Cassetta et al. identify a breast cancer tumor-associated macrophage (TAM) transcriptome that is different from those of monocytes and tissue-resident macrophages, and which is associated with shorter disease-specific survival, and they demonstrate crosstalk between tumor cells and TAMs via SIGLEC1, CCL8, and CSF1.