Background: The aim of the present study was to determine the predictive/prognostic value of the secreted protein, acidic and rich in cysteine (SPARC) in cases of unresectable, locally advanced, non-small cell lung cancer. Materials and Methods: The study included 84 patients with Stage IIIA-B non-small cell lung cancer, undergoing simultaneous chemoradiotherapy including radiotherapy at a dose of 66 Gy and weekly docataxel (20 mg/m(2)) and cisplatin (20mg/m(2)). SPARC expression was studied in biopsy material by immunohistochemical methods and correlations with treatment responses or survival were evaluated. Results: Median overall survival was 16 +/- 2.73 (11.55-20.46) months for low expression vs 7 +/- 1.79 months (7.92-16.08) months for high expression (p=0.039), while median local control was 13 +/- 2.31 (8.48-17.5) months for low expression vs 6 +/- 0.85 (4.34-7.66) months for high expression (p=0.045) and median progression-free survival was 10 +/- 2.31 (5.48-14.5) months for low expression vs 6 +/- 1.10 (3.85-8.15) months for high expression (p=0.022). In both univariate and multivariate analyses, high SPARC expression was associated with significantly shorter overall survival (p=0.003, p=0.007, respectively), local control (p=0.008, p=0.036) and progression-free survival (p=0.004, p=0.029) when compared to low SPARC expression. No significant difference was detected between high and low SPARC expression groups regarding age, sex, T stage, N stage, histopathology and stage-related patient characteristics. Conclusions: High SPARC expression was identified as a poor prognostic factor in cases with locally advanced NSCLC treated with concurrent chemoradiotherapy.