Rationale: Triggering receptor expressed on myeloid cells 1 (TREM-1) is a molecule crucial for the triggering and amplification of inflammatory response and a new biomarker for sepsis. Tumor-associated macrophages and inflammation in tumor microenvironment are also involved in cancer progression. Objectives: To determine the role of TREM-1 in tumor-associated macrophage and cancer progression. Methods: Using enzyme-link immunosorbent assay (ELISA) and Western blot, we measured soluble TREM-1 (sTREM-1) level in 65 pleural effusions of various etiologies. We evaluated TREM-1 positive cells by immnocytochemistry in malignant pleural effusion and in lung tumor versus adjacent normal tissue in surgical specimens from 68 NSCLC patients. TREM-1 expression was correlated with patient survival. TREM-1 expression in primary isolated peripheral blood macrophages co-cultured with lung cancer cell-lines was determined by quantitative real-time RT-PCR. Measurements and Main Results: sTREM-1 and tumor- associated macrophage TREM-1 expression were increased in malignant pleural effusions in non-small cell lung cancer (NSCLC) patients. Lung cancer cells could directly up-regulate TREM-1 and pro-inflammatory cytokines (tumor necrosis factor- (TNF-), interleukin-1 (IL-1)) expression in primary isolated peripheral blood macrophages in co-culture experiments. Increased TREM-1 positive tumor-associated macrophages in tumor tissue of NSCLC patients were associated with reduced disease-free (P=0.011) and overall survival (P=0.004). Multivariate Cox regression analysis indicated that TREM-1 was an independent predictor of patient survival (HR= 2.72, 95% CI=1.33 to 5.57, P=0.006). Conclusions: Cancer cells can directly up-regulate TREM-1 expression in patients' macrophages. TREM-1 expression in tumor-associated macrophages is associated with cancer recurrence and poor survival of NSCLC patients. TREM-1 and the inflammatory response may play an important role in cancer progression.