With the development of imaging technology, an increasing number of synchronous multiple lung cancers (SMLCs) have been diagnosed in recent years. Patients with >1 tumor are diagnosed with either synchronous multiple primary lung cancers (SMPLCs) or other primary tumors and metastases. Clinical guidelines, histological characteristics, and molecular diagnostics have been used to discriminate SMPLCs from other multiple lung cancers. However, there is still ambiguity in the diagnosis of SMPLCs of the same histological type. We enrolled 24 patients with the same histological type of SMLCs and assessed their status using established clinical guidelines, comprehensive histological subtyping, and molecular analysis. The sum value of the differential microRNA (miRNA) expression profiles (ΔΔCt) with matched tumors was evaluated to discriminate SMPLCs of the same histological type from metastases. Twelve patients with lymph node metastases were included for comparison, and the sum value of the ΔΔCt of 5 miRNAs between primary tumors and lymph node metastases was <9. Patients definitively diagnosed with SMPLCs by integrated analysis were also classified as SMPLCs by miRNA analysis; 6 patients showed conflicting diagnoses by integrated and miRNA analysis and 14 were given the same classification. Analysis of miRNA expression profiles is considered to be a useful tool for discriminating SMPLCs from intrapulmonary metastases.