Chemoprevention strategies to prevent the development of lung cancer in at-risk individuals are a key component in disease management. In addition to being highly effective, an ideal chemopreventive agent will require low toxicity as patients are likely to require treatment for several years before their risk of cancer is lowered to background levels. In principle, a combination of safe agents that work through distinct mechanisms will improve efficacy while simultaneously maintaining a favorable safety profile. Here, we describe the use of the decaffeinated green tea extract Polyphenon E (Poly E) (1% in diet) and aerosolized difluoromethylornithine (DFMO) (20 mg/kg/day, 5 days/week) in a mouse lung cancer chemoprevention study using a progression protocol. Female A/J mice were injected with benzo[a]pyrene (B[a]P) at 8 weeks of age and precancerous lesions allowed to form over a period of 21 weeks before chemoprevention treatment for an additional 25 weeks. Poly E treatment did not significantly inhibit average tumor multiplicity but reduced per animal tumor load. Analysis of tumor pathology revealed a specific inhibition of carcinomas, with the largest carcinomas significantly decreased in Poly E-treated animals. Aerosolized DFMO did not have a significant effect on lung tumor progression. Magnetic resonance imaging of B[a]P-induced lung tumors confirmed the presence of a subset of large, rapidly growing tumors in untreated mice. Our results suggest a potential role for green tea extracts in preventing the progression of large, aggressive lung adenocarcinomas.