The CCAAT/enhancer-binding protein-alpha (CEBPA) is a transcriptional factor that plays a crucial rolein the control of proliferation and differentiation of myeloid precursors. This gene was recognized as the targetof genetic alterations and were associated with clinical complexity among AML. We here analyze the frequencyand types of CEBPA mutations and polymorphisms in a de novo AML patients from South India and tried tofind out associations of these variations with different clinical parameters and the prognostic significance inAML. Study was carried out in 248 de novo AML patients, cytogenetic analysis was performed from the bonemarrow samples and was karyotyped. PCR-SSCP analysis and sequencing was performed for the detection ofCEBPA gene variations. All the statistical analysis was performed using SPSS 17 (statistical package for socialsciences) software. Pearson Chi-square test, Mann-Whitney U test, Kaplan-Meier survival analysis and log ranktests were performed. CEBPA mutations were detected in 18% and CEBPA polymorphisms were detected in18.9% of AML cases studied. Most of the mutations occured at the C terminal region. Polymorphisms weredetected in both N and C terminal region. with most common being, c.584_589dup ACCCGC and c.690G>T. Asignificant association was not observed for the mutation and polymorphism with respect to clinical and laboratoryparameters. Survival advantage was observed for the mutated cases compared to non mutated cases, especiallyfor the normal karyotype groups. Polymorphisms has no effect on the survival pattern of AML patients. CEBPAmutation and polymorphisms were observed with similar frequency and was identified in all the FAB subtypesas well as in cytogenetic risk groups in our study population, but CEBPA mutations alone confer a prognosticvalue for NK AML patients.