The omics era made possible the quest for efficient markers for cancer progression and revealed that macrophage populations are much more complex than just the M1/M2 dichotomy. Complement C1q pops up as a marker of a tolerogenic and immunosupressive macrophage populations in both healthy and tumor tissues, but the specific role of C1q+ tumor associated macrophages is poorly understood. C1q is co-expressed in healthy and tumor macrophages with HLA-DR, APOE and MRC1 (CD206), suggesting a resident origin of this population. Tumor associated macrophages expressing C1q correlate with T cell exhaustion and poor prognosis in numerous cancers. Herein, we discuss the plural roles of C1q in these macrophages and how it could drive cancer progression.