By combining suppression subtractive hybridization and microarray to examine gene expressions between metastatic and non-metastatic non-small cell lung cancer (NSCLC), we have identified differential expression spectra of matrix metalloproteinases (MMP). Among MMPs, expressions of MMP-13, -14, -15 and -24 decreased, those of MMP-9, -11, -12, -16, -17, -19 and -23B did not change, and those of MMP-1, -2, -7, -8 and -10 increased dramatically. Overexpressions of MMP-1, -2, -7 and -10 were confirmed by reverse transcription-polymerase chain reaction. In this study we further assessed the clinical significance of MMP-1, -2, -7 and -10. Specimens from 472 patients with completely resected NSCLC were examined by immunohistochemistry. The median follow-up period was 38 months (range, 2-113 months). Overexpression of MMP-1 was observed in 72.9% (n=344) of 472 patients, that of MMP-2 was 77.9% (n=352), MMP-7 63.3% (n=299) and that of MMP-10 was 27.1% (n=128). For patients with lymph node metastasis, MMP-1 and -2 overexpressions were not only independent prognostic factors for unfavorable outcome, but also associated with decreased survival (p=0.0015, and p=0.011 respectively). The present study showed that MMP expression spectrum in NSCLC was heterogeneous: expression of some MMP increased, some unchanged, while some decreased. Therefore, it should be worth determining MMP expression pattern as a regimen reference for NSCLC patients who were scheduled to receive MMP inhibitor, which was class-specific, as adjuvant therapeutic agent.