Laryngeal squamous cell carcinoma (LSCC) demonstrates increasing rates worldwide due to viral-related (High Risk Human Papilloma Virus-HR HPV) persistent infection, cigarette and alcohol consumptions. Gross chromosomal alterations and specific gene aberrations-such as amplifications, deletions, point mutations-combined or not with epigenetic changes are responsible for the progressive transformation of normal squamous epithelia to their malignant phenotype. Among oncogenes that are implicated in the development and progression of LSCC, mouse double minute 2 homolog / murine double minute 2 (mdm2) seems to be an interesting marker for the biological behavior of the malignancy. Mdm2 is a proto-oncogene (gene locus: 12q14.3), encodes for a nuclear-localized E3 ubiquitin ligase, and acts as a major negative regulator in p53-mdm2 auto-regulatory pathway. Mdm2 directly binds to p53 and represses its transcriptional activity and promotes p53 proteasomal degradation. Aberrant mdm2 overexpression is a frequent observation in breast carcinomas, whereas there are limited data regarding LSCC. In the current molecular review we explored the role and specific aspects of mdm2 gene in LSCC.