It is well-known that the plasma level of group IIA phospholipase A2 (sPLA2-IIA) is increased in patients with malignant diseases, but whether the up-regulated enzyme expression is directly related to tumorigenesis or a consequence of tumor-associated inflammation remains unresolved. In this study we analyzed circulating levels of sPLA2-IIA, C-reactive protein (CRP), fibrinogen, factor VIII (FVIII), von Willebrand factor (vWF), and antithrombin as biomarkers of inflammation and coagulation in patients with various types of malignancies. Underlying tumor entities were lung, esophageal, gastric, pancreatic, colorectal, head and neck, and hepatocellular carcinomas as well as multiple myeloma and non-Hodgkin's lymphoma. Plasma levels of sPLA2-IIA are shown to be markedly increased in all types of analysed malignancies in comparison to the normal range (22.8 ± 4.5 μg/L versus <1.9 μg/L). Levels of sPLA2-IIA correlate positively with CRP (p < 0.001), fibrinogen (p < 0.01), FVIII (p < 0.05), and vWF (p < 0.05) and negatively with antithrombin levels (p < 0.05). Kaplan-Meier analyses revealed a statistically prolonged survival time of patients with lower sPLA2-IIA concentrations (<4 μg/L) in comparison to those with elevated concentrations (>4 μg/L) of this enzyme. In conclusion, the study shows that the measurement of plasma sPLA2-IIA levels has prognostic values in patients with different types of malignancies. The association of sPLA2-IIA levels with CRP, fibrinogen, FVIII, and vWF levels supports the importance of inflammatory processes for the up-regulation of sPLA2-IIA during cancer progression.