PURPOSE: Metastatic spread depends critically upon the invasiveness of tumor cells, i.e. their ability to breach basement membranes by elaborating and secreting specific proteolytic enzymes such as gelatinase A (MMP-2). Phospholipase D (PLD) is believed to play an important role in cell proliferation and tumorigenesis. Also several studies suggested that activation of PLD and consequent generation of phosphatidic acid are involved in signal propagation pathway leading to induction of MMP-2. However, the relation between PLD and MMP-2 is not fully studied in lung cancer tissue, yet. MATERIALS AND METHODS: Adenocarcinomas of the lung from 20 patients were studied for immunohistochemical expressions of PLD, MMP-2 and TIMP-2 to assess their diagnostic and prognostic importance in lung tumors. RESULTS: With decreasing tumor differentiation, there was a progressive increase of MMP-2 and PLD and TIMP-2 expression decreased. Type IV collagenase expression was significantly associated with the presence of lymph node metastases, with moderate to strong expression, presented in 60% node positive tumors compared with none of the node negative tumors (p < 0.05). PLD was increased in tumor (strong: 60%) with nodal metastases compared with those without nodal metastases (p < 0.05), Increase of MMP-2 and PLD expression was associated with loss of TIMP-2 expression. CONCLUSION: In correlation expression of the immunohistochemical markers and invasion, PLD as well as type IV collagenase and TIMP2 expressions was found to be a predictor of invasiveness. Measurable alterations in MMP-2 and TIMP-2 and in particular, expression of PLD may be an important factor to assess invasiveness in resectable adenocarcinoma of the lung.