Objective: It has been reported that 80% of all breast carcinoma cases are invasive ductal carcinoma (IDC), and 45% to 78% of invasive breast carcinoma cases are associated with ductal carcinoma in situ (DCIS). Therefore, it is important to gain insights into transcriptome changes that occur during DCIS progression to IDC. Methods: We downloaded Gene Expression Omnibus databases GSE21422 and GSE3893, and performed differentially expressed gene (DEG) analysis and cluster analysis, followed by pathway enrichment analysis and Oncomine analysis. Results: Twenty-six conserved DEGs were identified in both GSE21422 and GSE3893. These genes are mainly enriched in intermediate filament-based processes, immune responses, Staphylococcus aureus infection response, and phagosomes. Among them, FCGR2A, HLA-DRA, C3AR1, and FYB were reported to be involved in DCIS progression to IDC. High expression of HLA-DRA, C3AR1, and FYB in different types of breast cancer was validated using different Oncomine datasets. Moreover, elevated HLA-DRA and FYB levels were associated with breast cancer recurrence. Importantly, the overexpression of FYB was correlated with breast cancer metastasis. Conclusions: This study revealed the molecular characteristics associated with progression from DCIS to IDC. It also identified potential biomarkers for DCIS progression to IDC, which will aid breast cancer diagnosis and prevention.