A significant macrophage population has been detected within almost all human and mouse tumors. These tumor-associated macrophages (TAMs) are critical regulators of the tumor microenvironment and directly affect multiple steps in tumor development, including the growth, survival, invasion, and metastasis of tumor cells. Macrophages are highly versatile, multifunctional cells, and their phenotype closely depends on the physiological or pathological context. In response to microenvironmental signals, macrophages undergo different activation, including the ‘classic’ pro-inflammatory phenotype (also called M1) and the ‘alternative’ activated M2 polarization associated with an anti-inflammatory profile (Mosser, 2003). Classically activated M1 macrophages and alternatively activated M2 macrophages represent two extreme macrophage phenotypes. TAMs closely resemble ‘alternative’ (M2) macrophages, which produce high amounts of interleukin (IL)-10 but not IL-12, express scavenger receptors, and exhibit anti-inflammatory and tissue repair functions (Sica et al., 2008). In contrast, M1 macrophages, activated by interferon (IFN)-γ or other microbial products, produce large amounts of pro-inflammatory cytokines, express high levels of major histocompatibility complex molecules, and are potent killers of pathogens and tumor cells (Mills et al., 2000). The molecular mechanisms underlying TAM polarization to different phenotypes are the focus of intense investigation. Here, we present the first evidence that microRNA-155 (miR-155) is akey molecule controlling macrophage polarization. We found that the overexpression of miR-155 could re-program anti-inflammatory, pro-tumorial M2 TAMs to pro-inflammatory, antitumor M1 macrophages.