By considering this scenario, it doesn’t seem realistic to foresee any marked improvement in the survival of patients with NSCLC in the coming years, even in those with resectable disease. However, if we look at the natural history of operated NSCLC, we have to consider that the pattern of failure depends on the stage of the disease. The local control is, in fact, very satisfactory in stages IA-B,4,20whereas more advanced stages carry a higher risk of local recurrence. In particular, the recurrence rate is relatively low in stage II,21but increases in stage IIIA, especially in N2 disease.22–23 Overall, distant metastatic spread has to be considered as the leading cause of treatment failure in resected NSCLC. As a consequence, it is reasonable to hypothesize that the prevention of the metastatic spread (preoperatively, perioperatively, and postoperatively) could represent the mainstay of improvement in chances of cure in these patients. The process of metastatic colonization by the primary tumor involves several distinct steps and mechanisms, but it is well known that the components involved in blood clotting contribute to the systemic spread and/or successful implantation of metastatic cancer cells, but probably through different mechanisms.24We therefore believe that a strong rationale supports the investigation of drugs possibly inhibiting metastatic spread via the interference in the blood-clotting pathway. What is more, both unfractioned heparin (UH) and low-molecular-weight heparin (LMWH) seem to favorably affect the outcome of patients with cancer receiving prophylaxis or treatment of deep venous thrombosis.25–26 Although it is possible that the favorable impact on survival is related to the antithrombotic mechanisms, there is sufficient experimental and preclinical evidence that both UH and LMWH have an anticancer effect via different mechanisms.24–26 We therefore suggest that trials on long-term administration of LMWH in patients with operable NSCLC should be initiated as soon as possible, in the attempt to improve the outcome of this neoplasm, whose prognosis continues to be unsatisfactory (except in stage IA disease) in spite of complete resection and, possibly, adjuvant or neoadjuvant treatments.