The preoperative serum levels of tumor necrosis factor (TNF), soluble receptors for TNF (55- and 75-kDa sTNFr), and soluble CD14 (sCD14) were retrospectively measured in 66 patients with epithelial ovarian cancer and in 59 patients with benign ovarian masses. The preoperative serum TNF and sCD14 levels were higher in patients with epithelial ovarian cancer than in those with benign ovarian disease (P = 0.001 and P < 0.0001, respectively). Among patients with advanced malignancy, preoperative serum TNF and sCD14 correlated with neither the common prognostic variables nor the clinical outcome of patients. The preoperative serum 55- and 75-kDa sTNFr levels were higher in patients with epithelial ovarian cancer than in those with benign ovarian disease (P < 0.0001 and P = 0.02, respectively). Among patients with advanced malignancy, preoperative serum 55- and 75-kDa sTNFr correlated with FIGO stage (IV vs III, P = 0.008 and P = 0.01, respectively) and with the clinical outcome of patients. Among patients followed after surgery and chemotherapy for advanced epithelial ovarian cancer, 55- and 75-kDa sTNFr levels were significantly higher in the samples drawn from patients with clinical evidence of disease when compared to those from patients without clinical evidence of disease; conversely, TNF and sCD14 levels were similar in the two groups. In conclusion, the preoperative serum levels of TNF, 55- and 75-kDa sTNFr, and sCD14 were significantly higher in patients with epithelial ovarian cancer than in those with benign ovarian disease. The measurement of serum TNF and sCD14 seemed to be of limited clinical value for the management of patients with advanced epithelial ovarian cancer. Conversely, the assay of serum 55- and 75-kDa sTNFr might have a potential clinical relevance, for both prognostic purposes and assessment of disease status.