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Elevated plasma concentrations of the C-reactive protein (CRP) are frequently found in patients with malignant diseases. Discrimination between infection and noninfectious acute-phase reactions is essential for therapeutic decisions.Because increased procalcitonin (PCT) concentrations have been described predominantly in patients with a systemic infection, PCT plasma concentrations were measured prospectively in 111 patients with a hemato-oncological condition with a CRP concentration >8 mg/L.Documented cases of infection were identified in 42 patients, 39 patients had unexplained fever, and 30 patients had no signs of infection. Twenty patients in the latter group were classified as having an elevated CRP concentration caused by a high tumor load (tumor group), and 8 had elevated concentrations that were drug related (drug group). Median CRP concentrations did not differ significantly between groups of patients with and without infection. PCT concentrations were higher in patients with an infection than in patients without an infection and were within the normal range in all patients in the drug and tumor groups. As shown by receiver operating characteristic analysis, PCT concentration was a significant discriminator between having and not having infection, having infection and being in the tumor group, and having infection and being in the drug group. In contrast, CRP concentration was only a predictor of being in the drug group, when the cut-off point was set at 85.1 mg/L, which limited its clinical applicability.PCT concentration contributes significantly to the differential diagnosis for elevated CRP concentrations in patients with hemato-oncological conditions and facilitates therapeutic decisions.