Aim: Pancreatic cancer is estimated to be the 12th most common cancer in men and the 11 most common in women worldwide. Materials and Method: As other cancers, pancreatic ductal adenocarcinoma (PDAC) accumulates genetic alterations in oncogenes and suppressor genes. In the present study, we analyzed five biomarkers status: Epidermal growth factor receptor (EGFR) and p53 using immunohistochemical labeling in 39 PDAC and Kras, Nras, and Braf, using pyrosequencing in 25 normal pancreatic tissues, 25 pancreatic intraductal neoplasia (PanIN), and 39 PDAC. Result and Discussion: Abnormal immunolabeling of p53 and EGFR was detected in 97.4% and 71.8%, respectively. There was a statistically significant progressive increment (P < 0.001) in the percentage of mutated cases through normal pancreas (8%), PanIN-1A (28.6%), PanIN-1B (33.3%), PanIN-2 (60%), and PanIN-3 (85.7%) to PDAC (94.8%). These mutations were arising in codons 12 and 61 of Kras and in codon 600 of Braf. Most frequent mutations were G12D (46%), G12A (23%), and G12V (18%) of Kras. No mutations were found in codons 13, 59, 117, and 146 of Kras or in codons 12, 13, 59, 61, 117, and 146 of Nras. Conclusion: We confirm that EGFR, Kras, and p53 are the most frequent altered biomarkers in PDAC with difference in predominated Kras mutations subtypes. [ABSTRACT FROM AUTHOR]