Background <p>The pathological response in rectal cancer treatment provides insight into the molecular mechanisms, including genetic alterations and signaling pathways that influence tumor behavior and resistance to treatment.</p> Case Presentation <p>This report describes a 34-year-old Iraqi male diagnosed with stage III rectal cancer who achieved a complete pathological response following treatment with oxaliplatin-based chemotherapy. Notably, this outcome was achieved without the administration of chemoradiotherapy or the occurrence of neurotoxicity despite the efficacious cumulative‑dose administration (1700&#xa0;mg/m²) of oxaliplatin. Genomic analysis revealed the presence of a heterozygous (Ile/Val) genotype in the <i>GSTP1</i> gene, which may have contributed to the observed treatment response.</p> Conclusions <p>Genetic biomarkers play a crucial role in refining treatment strategies by enabling a more precise selection of patients who may safely forgo radiotherapy, thereby minimizing its associated toxicities. Additionally, molecular profiling can help predict susceptibility to oxaliplatin-induced neurotoxicity, facilitating dose adjustments or alternative therapeutic approaches to enhance treatment tolerance and long-term quality of life. Our findings highlight the importance of molecular profiling in optimizing treatment strategies while minimizing toxicity, especially in situations where radiological assessments suggest residual disease or produce unclear results.</p>