With the broad application of high-resolution computed tomography (CT) and high rates of early lung cancer screening, the number of patients diagnosed with synchronous multiple primary lung cancer (sMPLC) has been increasing. It becomes of great prominence to distinct sMPLC from intrapulmonary metastases in clinical practice. An increasing number of studies have developed high-throughput sequencing based genetic approaches to specify the molecular characteristics of sMPLC, which contributes to a better understanding of its tumorigenesis. The genetic profile of sMPLC also benefits its diagnosis, which mainly relies on its clinicopathological criteria. Here, we summarize the progresses on the diagnostic criteria for sMPLC, and also molecular features of sMPLC from the perspective of clonality analysis.