Background: Pregnancy-associated plasma protein-A (PAPP-A) has insulin-like growth factor (IGF)-dependent IGFBP-4 protease activity and plays an important role in amplifying local IGF-1 activity in wound healing, vascular repair. and bone remodeling. We postulated that PAPP-A may contribute to the availability and activity of IGFs, which affect lung cancer. Therefore, we determined the levels of PAPP-A in patients with lung cancer and their possible clinical significance. Methods: The study population consisted of 83 patients with lung cancer and 33 healthy subjects as a control group. Serum PAPP-A levels were determined using an ultrasensitive enzyme-linked immunosorbent assay. Results: The serum PAPP-A levels were higher in patients with lung cancer [median (interquartile range) 10.7 (7.6-14.2) ng/mL] than in the control group [6.2 (5.2-9.8) ng/mL, P < 0.001]. There was a significant negative correlation between the serum PAPP-A levels and Karnofsky performance status (r = -0.330; P < 0.001) and a positive correlation with patient age (r = 0.358; P < 0.001). Conclusion: PAPP-A is a proatherosclerotic metalloproteinase that is also thought to be an inflammatory marker. We found that the serum PAPP-A levels increased in patients with lung cancer and postulated that PAPP-A levels may be a prognostic factor in such cases.