Lung cancer is an inflammation-associated epithelial carcinoma. A highly active interleukin 6 (IL-6)/glycoprotein 130 (gp130)/signal transducer and activator of transcription 3 (STAT3) pathway has been identified in a subset of primary lung cancer and closely correlated with tumor progression and poor prognosis. In a previous study, the frequent occurrence of somatic gain-of-function mutations was observed in the gp130-encoding IL6ST gene in exon 6 in 60% of inflammatory hepatocellular adenomas. Prompted by this finding, we assessed 110 Chinese lung carcinomas using PCR and direct DNA sequencing but found no somatic mutation of IL6ST in exon 6. However, one new potential germline missense mutation c.599C>G was identified in one adenocarcinoma that harbors wild-type epidermal growth factor receptor and KRAS. Protein modeling analysis showed that this mutation might not affect the gp130 protein conformation. Moreover, activated STAT3 was observed in most of the lung tumor tissues at a higher level than that in matched normal lung tissues. In conclusion, the c.599C>G mutation may be a new single nucleotide polymorphism of IL6ST, but mutations in exon 6 of this gene are not apparently common genetic variations occurring and leading to constitutive activation of STAT3 in lung cancer.