Various genetic mutations and biologic alterations occur during cancerization, which promote the malignant development of tumors. Multiple genes are involved in and cooperated with the occurrence and development of small cell lung cancer (SCLC). SCLC manifests early and frequent metastasis as well as ultimate poor response to chemotherapy. New therapies for SCLC based on understanding of molecular and cellular mechanism of transformation are needed. SCLC is associated with multiple chromosomal abnormalities, the most common of which is chromosome 3p deletion, as well as abnormal oncogenes and tumor suppressor genes. Along with the genetic alterations, SCLC overexpresses various cell surface receptors, such as receptor tyrosine kinase (RTKs), G-protein-coupled receptors, integrins, and so on. Some activated downstream molecules, such as phosphatidylinositol 3'kinase, would serve as good candidates for therapeutic targets.