Cancer is one of the leading causes of death worldwide, with approximately 10 million cancer-related deaths reported in 2020. Approximately 70% of these deaths occurred in developing countries. In 2020, 2.3 million women were diagnosed with breast cancer and 685,000 deaths due to breast cancer were reported worldwide. Cancer is characterized by the presence of most triggers in the genome. Mutations in genes, either passed from one generation to the next or acquired throughout life, can cause breast cancer. Tumor suppressor genes encode proteins that negatively regulate cell proliferation and repress certain oncogenes. One of these genes, the <I>TP53</I> gene, has multiple biological functions. Understanding the mechanism of action of p53 in breast carcinogenesis has been an important challenge in cancer research. This study aimed to investigate the involvement of alterations in exon 4 of the <I>TP53</I> gene in Mauritanian patients with breast cancer. The study was conducted using 45 tumor tissue sequences and 35 control sequences. The nature and position of the mutations were determined using Mutation Surveyor V5.1.2 The pathogenicity of the mutations was determined using Polyphen2, SIFT, and Mutation Tester, and their three-dimensional structure was determined using the I-Tasser server. DnaSP version 5.10, MEGA version 7.014, and Arlequin version 3.1 were used to highlight the variability of exon 4 of the <I>TP53</I> gene. Our results revealed the presence of a single-nucleotide variant at position (c.139 C>T), which causes an amino acid change from proline to serine at codon 47 in the coding region of exon 4 of the <I>TP53</I> gene. Of note, this variant has already been listed in the database (rs1800371). In addition, five novel mutations were found in the cancer tissue sequences alone, with statistically significant scores. Analyses of genetic variability indicated a relatively high polymorphism in tumor tissue sequences compared with control sequences. This variability may contribute to the involvement of exon 4 mutations in the occurrence of breast cancer in our population, and serves as the first data on <I>TP53</I> exon 4 alterations in Mauritania.