Non Hodgkin Lymphoma (NHL) is a malignant neoplasm of lymphoid cells, considered the third most common malignancy in Oman. Number of factors such as infection, immunosuppression, genetic and environmental factors can contribute to increase the risk of NHL. Among the NHL different subtypes, Diffuse Large B-Cell Lymphoma (DLBCL) is the most common worldwide and accounts for 40%, whereas in Oman and other developing countries it accounts for about 60% of NHL. DLBCL is an aggressive form of NHL characterized by heterogeneous morphology, phenotype, molecular and outcomes. Several tumors including NHL have been reported to harbor p53 mutations within a highly conserved region of the gene, Transformed cases of DLBCL (t-DLBCL) apparently display the highest rate of P53 mutations. We screened for p53 mutations in an Omani cohort of patients with DLBCL using PCR and sequence analysis on archival paraffin embedded material to validate previous immunohistochemistry data. Twenty three formalin fixed paraffin embedded tissue blocks and 21 blood samples from patients with DLBCL were processed for DNA analysis. An additional ten samples from individuals with no history of DLBCL were used as controls. DNA extraction from paraffin embedded tissues was performed using the phenol/chloroform method. Exons 4 to 9 of the p53 gene were amplified and subjected to sequence analysis. Furthermore, immunohistochemistry using an antibody cross reacting with both mutant and wild type p53 was performed. Sixty two percent (13/21) of blood samples showed a polymorphism in codon 72 (SNP72) of exon 4, whereas in control samples it was found in 90% (9/10) of the cases (p=0.086). Eight cases from paraffin embedded material showed deletion in p53, three of which were t-DLBCL. Two cases (2/23) showed missense mutations leading to Val 143 Leu, Leu 145 Thr, Try 146 Arg and Thr 150 Arg amino acid changes. No aberration was detected in the remaining 13 patients. Sixteen cases (69.5%) were stained positively using immunohistochemistry analysis, suggesting the presence of mutant type of p53 protein, Deletions in p53 gene were found to be common aberration in this study while immunohistochemistry displayed a higher percentage of p53 mutation. SNP72 was not found to be associated with development of DLBCL.