Back ground: Pleural effusion remains a diagnostic challenge. A number of tumor markers might facilitate the identification of patients with malignancies. Objective: To assess the value of Dikkopf-1 concentrations in both serum and pleural fluid in the differentiation between malignant and non malignant pleural effusions. Methods: 47 patients with pleural effusions were enrolled in the study. They were classified into two groups: group I: 24 patients with malignant effusions, group II: 23 patients with non malignant effusions. Thoracentesis with biochemical, cytological and bacteriological examination of pleural fluid and determination of Dikkopf-1 level in serum and pleural fluid were done. Results: Serum and pleural levels of DKK-1 were significantly higher in the malignant group compared with the non-malignant group. At cut off point 3091 pg/ml serum DKK-1 shows 100% sensitivity and 91.3% specificity while at cut off point 4607 pg/ml pleural DKK-1 levels showed 100% sensitivity and 100% specificity. In the non malignant group, serum and pleural levels of DKK-1 were significantly higher in TB patients compared to pneumonia and liver cirrhosis. Conclusions: Malignant effusions are associated with elevated serum and pleural DKK-1 level but it cannot be used as sure marker for the diagnosis of malignancy since it rises in many other conditions.