The courses of circulating nucleosomes in the serum of patients with various solid tumors correlate with the clinical outcome after chemo- and radiotherapy. Already during the initial phase of treatment they showed considerable alterations consisting of a rapid increase followed by a decrease during the first therapeutic week. Among patients with advanced lung cancer undergoing chemotherapy, those patients who responded to therapy exhibited less pronounced increases and more complete decreases compared to those patients with insufficient response. In addition, response to therapy was correlated with stronger decreases of the precyclic baseline values from cycle 1 to 2 and from cycle 1 to 3. Thus, circulating nucleosomes are a valuable tool for the early prediction of therapeutic efficacy and can help to modulate therapy strategies early and on an individual basis.