We examined the molecular biological differences among LC cases, with and without smoking, and with or without COPD. Formalin-fixed paraffin-embedded blocks from 36 patients of lung adenocarcinoma that had undergone surgical resection from 2006 to 2009 were examined immunohistochemically for six proteins[AChR M3, ChAT, STAT3, survivin, HIF-1α, and IL-6]considered to modulate signal transduction pathways in cancer cells. The expression levels of AChR M3, and ChAT were significantly higher in smokers with COPD than those without COPD. The expression of STAT3 was significantly higher in non-smokers than smokers. Survivin expression tended to be higher in non-smokers than smokers(P=0.068), albeit insignificantly. The results showed differences in the expression of cholinergic signaling pathway and JAKSTAT pathway components among patients with lung adenocarcinoma, in smokers and non-smokers and with/without COPD. These results could contribute to the treatment of recurrence, and also help to identify targets for cancer prevention strategies.