BACKGROUND/AIM: Heat-shock protein 90 (HSP90) is a molecular chaperone that stabilizes many client proteins in normal and cancer cells, and approximately 3% of intracellular HSP90 is located in the nucleus. HSP90 is also targeted for the treatment of advanced non-small cell lung cancer (NSCLC). This study aimed to elucidate the clinical role of nuclear HSP90 levels in tissues from patients with NSCLC. MATERIALS AND METHODS: Nuclear and total HSP90 levels were assessed using immunohistochemistry. RESULTS: Multivariate logistic regression showed that the total HSP90 level was independently positively associated with age (p=0.041) and tumor histology of squamous type (p=0.007). By contrast, nuclear HSP90 level was independently positively associated with higher performance score (p=0.011), ever-smoking history (p=0.006) and presence of lymph node (p=0.036) or distant (p<0.001) metastasis, but not age or tumor histology. The level of nuclear HSP90, but not total HSP90, was negatively correlated with patient survival time (p<0.001). CONCLUSION: Nuclear accumulation of HSP90 might be a predictor of metastasis and survival in patients with NSCLC.