Objective: The skeleton is one of the most frequent sites for metastases from lung cancer. However, bone lesions may be overlooked and often are not diagnosed until they manifest as bone pain or skeletal-related events. Several studies have shown the potential of using serum miRNAs as a non-invasive biomarker for cancer patients. We investigated serum miRNAs that may serve as biomarkers to differentiate between lung adenocarcinoma patients with and without bone metastasis. Methods: Five miRNAs associated with metastasis (miR-21, miR-146a, miR-148a, miR-328 and miR-378) were selected through literature review. We examined these serum miRNAs concentrations by quantitative real-time reverse transcription- polymerase chain reaction from clinically matched 19 patients with bone metastasis and 13 without bone metastasis. Results: The initial analysis showed that miRNAs were stable and detectable in all serum samples. The serum concentrations of miR-21, miR-146a and miR-378 were significantly higher in bone metastasis than no bone metastasis (p=0.037, 0.041 and 0.037, respectively).The values of the area under the ROC curve were 0.721 for the miR-21 assay (p=0.023), 0.717 for the miR-146a assay (p=0.027) and 0.721 for the miR-378 (p=0.032). Conclusion: The present study suggests that circulating miRNAs may be a specific indicator of bone metastasis detection in advanced lung adenocarcinoma. Further large-sampled studies will be required to validate the definite role of serum miRNAs and related metastatic sites.