MDR1 hypermethylation plays an important role in pathogenesis and progression of neuroblastoma tumors. This hypothesis was tested by studying the methylation status of MDR1 gene promoter in neureoblastoma biopsy specimens during the progression of tumor from stage-1 to stage-4. Results of our findings demonstrate an inverse correlation between the methylation status of MDR1 promoter and MDR1 expression during the progression of disease from stage-1 to stage-4 as determined by methylation specific PCR (MSP) and RT/PCR analyses. The results of the RT/PCR and MSP analyses were validated by quantitative Real Time PCR analysis. Data from present study suggest that transcriptional inactivation of MDR1 gene due to increased MDR1 promoter methylation may be a contributing factor in pathogenesis and progression of neuroblastoma tumors, and may be used in designing an effective treatment therapy to neuroblastoma patients.