The Leucine rich repeat containing G protein coupled receptor 5 (LGR5), may be a candidate marker of non-small cell lung cancer (NSCLC) cells with stem cell-like properties. Aldehyde dehydrogenase 1A1 (ALDH1A1) is one of NSCLC stem cell markers. To identify the relationship of LGR5 and ALDH1A1 in NSCLC, we analyzed the expression of LGR5 and ALDH1A1 in NSCLC samples, and determined their clinical significance. We performed quantitative RT-PCR for LGR5 and ALDH1A1 expression in 24 NSCLC patients, and showed that LGR5 and ALDH1A1 mRNA were frequently increased in NSCLC tissues in comparison to that in adjacent normal tissues (p = 0.0005 and p < 0.0001, respectively). Besides, the expression of LGR5 and ALDH1A1 mRNA has a significant correlation (r = 0.416, P = 0.0483). The expression of LGR5 and ALDH1A1 in 109 NSCLC tumors and 50 adjacent normal tissues were detected by immunohistochemistry. Positive LGR5 and ALDH1A1 expression was defined in 28.4% and 41.3% of the NSCLC tumors, respectively. Further analysis indicated that 24 of these LGR5(+) (24/31) samples expressed ALDH1A1(r = 0.3883, p < 0.0001), we also found co-localization of LGR5 and ALDH1A1 in tumor tissue samples. LGR5 and ALDH1A1 expression was significantly associated with higher pathological TNM stage of the disease (stage I + II and III + IV) (P = 0.0311 and p = 0.0221, respectively), the co-expression of LGR5 and ALDH1A1 was associated with nodal status (p = 0.0424). High expression of LGR5 or ALDH1A1 was related to poor prognosis (P = 0.0125 and p = 0.0410, respectively), and NSCLC patients with co-expression of LGR5 and ALDH1A1 had a poorer prognosis than the others (P = 0.0011). Both of them can be an independent risk factor of a poorer prognosis (P = 0.016 and P = 0.024, respectively). The expression of LGR5 and ALDH1A1 were closely associated with the tumorigenicity, metastasis and poor prognosis of NSCLC, and LGR5+ cells in NSCLC were likely to be the cancer cells with stem cell-like properties due to the significant correlation between LGR5 and ALDH1A1. (C) 2015 Elsevier Inc. All rights reserved.