Previously, we demonstrated that lipocalin-type prostaglandin D 2 synthase (L-PGDS) induces apoptosis and prevents cell cycle progression in several cell types. In this study we determined the expression of L-PGDS in a variety of human lung tumor types. While L-PGDS expression was evident in the surrounding margins, we observed significantly decreased protein and gene expression in the tumor tissue. Using RT-PCR we demonstrated that L-PGDS gene expression decreased proportionately with tumor progression. In addition, we demonstrated that exogenously added L-PGDS could suppress the hyperproliferation and PDGF-stimulated migration of A549 cells, a cultured carcinomic human alveolar basal epithelial cell line. We conclude that L-PGDS may play a key role in modulating lung cancer growth and may offer a novel diagnostic and therapeutic approach for treatment.