The inflammatory proteins S100A8 and S100A9 form a heterocomplex associated with the prognosis of various cancers. This study aims to examine the association between S100A8 and S100A9 expressions and various pathological variables in primary lung adenocarcinoma (AC). Serial paraffin-embedded tissue sections from 150 patients with lung AC resected at the Shizuoka General Hospital were immunostained and assessed. In patients with invasive lung AC (n = 132), an overlap between S100A8 and S100A9 immunopositivities was observed. S100A8 alone was not reported, but both immunopositivities were associated with high histological grade (P < 0.05), and S100A8 immunopositivity was associated with vessel permeation, poor pT categories, node metastasis, and poor pStage (P < 0.05). In patients with AC in situ (n = 18), only limited S100A9 immunopositivity was observed. The overexpression of S100A8 (S100A8/S100A9 up-regulation) might be a poor prognostic factor in lung AC.