Severe combined immunodeficiency (SCID) is characterized by impairment of both cellular and humoral immunity leading to death early in life due to infections. Mutations in recombination activating genes (RAG1/2) represent approximately 10% of all SCID cases; RAG1 and RAG2 play a vital role in the development of the T cell and immunoglobulin receptors. The aim of this study was to detect the frequency of RAG1 and RAG2 mutations among a cohort of Egyptian children diagnosed as SCID/OS and to shed light on the importance of molecular analysis of genetic basis of this condition. Twelve children diagnosed as SCID were enrolled in this study. Analysis of RAG1 and RAG2 genes was done by Sanger sequencing method. In our study we detected five mutations in RAG genes in four of our patients. It was concluded that mutations in RAG1/2 are not uncommon in Egyptian patients with SCID. Molecular diagnosis procedures are now available to determine the diagnosis or to serve as a tool for genetic counseling and prenatal diagnosis. We recommend that much work needs to be done to assess the prevalence of SCID-associated mutations and disease in our population and that genetic counseling and prenatal diagnosis are a method of choice to prevent disease.