Neutrophils are primary inflammatory cells and absolutely essential to protect the host during the early phases of microbial infection. Their role in cancer is less clear. Current evidence suggests that neutrophils show high functional plasticity and can adopt protumor and antitumor activity. Protumor neutrophils are functionally related to the recently described granulocytic myeloid-derived suppressor cells. We propose a model in which homeostatic chronic recruitment and activation of neutrophils result in mainly protumor activity. In contrast, therapeutic interventions in many cases elicit acute activation, enhance direct effector functions as well as indirect regulatory functions of neutrophils with potent antitumor activity. Conversion of protumor activity of neutrophils into antitumor activity by means of appropriate stimulation or modulation may offer new possibilities in biologic therapy of cancer.