Overexpression of P-glycoprotein (P-gp) has been identified by a variety of methods in NK cells and NK malignancies. The aim of this study was to determine the clinical significance of P-gp in previously untreated extranodal NK/T-cell lymphoma, nasal type. Tumor specimens from 30 patients initially treated with CHOP or CHOP-based chemotherapy were examined by immunohistochemistry using JSB-1, a monoclonal antibody recognizing the intracellular epitope of P-gp molecule. Twenty cases (67%) were positive for P-gp expression. The complete response rate achieved in P-gp positive patients was significantly lower than in P-gp negative ones (20% vs. 60%, P = 0.045). With a median follow-up of 25 months, the 2-year progression-free survival (PFS) and overall survival (OS) rates for all patients were 66 and 69%, respectively. Compared with both PFS and OS rates of P-gp positive patients, those of P-gp negative patients showed a trend of benefit that did not reach statistical significance for borderline P values (PFS: 90% vs. 54%, P = 0.1057; OS: 90% vs. 61%, P = 0.2028). Our results suggest that P-gp expression is related with poor treatment outcomes of extranodal NK/T-cell lymphoma, nasal type. Am. J. Hematol., 2008. © 2008 Wiley-Liss, Inc.