| Summary: | Small cell lung carcinoma (SCLC) is an aggressive and difficult to treat cancer. Although immunohistochemistry is not mandatory for a SCLC diagnosis, it might be required, especially in small samples. Insulinoma-associated protein 1 (<i>INSM1</i>) is expressed in endocrine and nervous tissues during embryogenesis, generally absent in adults and re-expressed in SCLC and other neuroendocrine neoplasms. Its high specificity propelled its use as diagnostic biomarker and an attractive therapeutic target. Herein, we aim to provide a systematic and critical review on the use of <i>INSM1</i> for diagnosis, prognostication and the treatment of SCLC. An extensive bibliographic search was conducted in PubMed<sup>®</sup> focusing on articles published since 2015. According to the literature, <i>INSM1</i> is a highly sensitive (75–100%) and specific (82–100%) neuroendocrine immunohistochemical marker for SCLC diagnosis. It can be used in histological and cytological samples. Although advantageous, its standalone use is currently not recommended. Studies correlating <i>INSM1</i> expression and prognosis have disclosed contrasting results, although the expression seemed to entail a worse survival. Targeting <i>INSM1</i> effectively suppressed SCLC growth either as a suicide gene therapy regulator or as an indirect target of molecular-targeted therapy. <i>INSM1</i> represents a valuable biomarker for a SCLC diagnosis that additionally offers vast opportunities for the development of new prognostic and therapeutic strategies.
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