ABSTRACT Introduction Breast cancer is a malignant tumor that originates in breast tissue and the most common cause of malignant tumors‐related death in women worldwide. Long noncoding RNA (LncRNA) is a transcribed RNA with more than 200 nucleotides in length but has no notable potential for protein coding. Hypoxia is a common occurrence in tumor microenvironments due to an imbalance in oxygen supply and consumption by rapidly growing tumors. The aim of study is to analyze the gene expression of different types of lncRNAs (lnc.4.2, lnc.4.3) as a molecular tumor marker in relation with hypoxia‐inducible factor 1alpha (HIF‐1α) gene and main clinic pathological characters for patients and healthy control group. Methods The study included 100 newly diagnosed cases of bc divided into four groups: ( n = 25) low grade before treatment (LBT), ( n = 25) low grade after treatment (LAT), ( n = 25) high grade before treatment (HBT), and ( n = 25) high grade after treatment (HAT). In addition, ( n = 25) as a control group. Results The results of this study showed that lncRNA 4.2 and lncRNA 4.3 exhibited strong discriminatory ability specifically in the LBT versus control and HAT versus control comparisons, with AUC values exceeding 0.70. This indicates that these lncRNAs may be particularly useful for distinguishing LBT and HAT samples indicate potential role in treatment response or the pretreatment state. HIF1A also exhibited moderate diagnostic potential in the HBT versus control and HAT versus control comparisons, with AUC values greater than 0.60. Its performance was notably better in the HBT group, where it achieved an AUC of 0.774, indicating good discriminatory ability in this specific context. This suggests that HIF1A may be a useful diagnostic marker for conditions associated with HBT samples, potentially reflecting its role in cellular stress response.