We report immunohistochemical staining results for cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 in primary tumors of 117 patients with resected adenocarcinoma of the lung (median follow-up, 20 months). For COX-2, we graded the degree of tumor staining according to the sum of staining intensity and the proportion of cells staining. For MMP-9, we used morphometry to quantify cytoplasmic staining. We used the Cox proportional hazards model to analyze overall survival. With only 29 patients censored at last follow-up, after controlling for the effect of pathologic stage, staining for COX-2 and MMP-9 and subtype of tumor were related significantly to survival (P < 6 x 10(-5)). The effects of COX-2 and MMP-9 were opposite. Whereas any staining for COX-2 decreased the hazard and increased survival time, increased staining for MMP-9 increased the hazard and decreased survival time. The results also suggested that staining for COX-2 decreases with dedifferentiation. Our results suggest that staining for the combination of COX-2 and MMP-9 and categorizing tumors into papillary and nonpapillary types may provide important prognostic information for patients with resected adenocarcinoma of the lung; it is possible that these 3 variables could aid decisions about postoperative adjuvant treatment.