non-melanoma skin cancers are the most common malignant neoplasms in humans. about 95% of all non-melanoma skin cancers are represented by basal cell carcinoma and squamous cell carcinoma. their prevalences are still increasing worldwide, representing an important public health problem. the genetic alterations underlying basal cell carcinoma and squamous cell carcinoma development are only partly understood. much interest lies in determining the genetic basis of non-melanoma skin cancers, to explain their distinctive phenotypes, biological behaviors and metastatic potential. we present here a molecular genetic update, focusing on the most frequent genes and genomic instability involved in the development and progression of non-melanoma skin cancers.