Here, we demonstrate that in SH2B1-expressing NSCLC cells, SH2B1 has a functional role in promoting proliferation by modulation of mitogen-activated protein kinase signaling, phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of Rapamycin (mTOR) signaling pathway and inducing an elevated level of the transcription factor cyclin D1. The gene discussed is SH2B1; the disease is non-small cell lung carcinoma.