Background and Objectives: Breast cancer (BC) is the most common invasive malignancy affecting women worldwide. The tumor-suppressor P53 gene (P53) is frequently mutated in breast tumors. To use P53 as a target for therapy, it is important to accurately assess p53 mutation status in tumor samples. Materials and Methods: A total of 102 tumor samples were collected from breast cancer patients referred to Tabriz hospitals between the 2007-2009 period. DNA was extracted by Proteinase K– Isopropanol method and then performed amplification and sequencing of P53 from exons 5 and 6. Results: Mutations in the P53 gene were detected in 17.6% of the patients. Including 7 polymorphisms (6.68%) and 11 mutations (10.78%). Overall, 18.2% of the mutations were found in codons 160 (ATG>AAG) and 163 (ATC>AAG) in exon 5. Also 81.8% of the mutations observed in exon 6: codon 193(CAT>AAT), codon195 (ATC>TTC), codon 195 (ATC>AAC), codon 198(GAA>TAA), codon 220 (TAT>TGT), codon 213 (CGA>CTA), and codon 214 (CAT>CG). No alteration observed in intron5 and all of polymorphism detected in 13399A>G nucleotide of exon 6. The majority of detected mutations are missense that located on DNA-binding domain of P53. This type of mutation usually leads to the production of a mutant protein with a compromised structure and altered DNA-binding capacity. Conclusion: This is the first report of its kind from the East Azarbaijan region. Our results indicate a rather high frequency of exon 6 mutations in P53 among patients with breast cancer. Furthermore, the mutation pattern appears differs from other regions. However, further studies are needed to determine the role of P53 mutations in breast cancer development.