Amplification of the MYC gene is reported to be associated with the development of head and neck squamous cell carcinoma (HNSCC). However, there are no data concerning whether the amplification is confined to the MYC gene itself or spans distant 5' and/or 3' regions of this gene in HNSCC as seen in different lymphomas, colon carcinoma, and uterine cervical carcinoma (CaCx). In this study, we analyzed the alterations (amplification/rearrangement) in the 580 Kb surrounding of the MYC gene to understand the status of this locus in primary HNSCC of Indian patients. The MYC alterations were analyzed by Southern blot using the pal-1/MYC/MLVI4 probes. The alterations in the MYC locus (adjacent region of the c-myc gene) were then correlated with the various clinicopathological parameters. The overall amplification involving the MYC locus was seen in 46% of the samples. The MYC gene, pal-1 region, and MLVI4 region were amplified in about 38%, 24%, and 20% of the samples, respectively. Some samples showed co-amplification encompassing pal-1-MYC-MLVI4 or pal-1-MYC or MYC-MLVI4 regions. No significant association was observed between the amplification in the MYC locus and the different clinicopathological parameters except for tumor differentiation. Thus, it seems that, similar to other tumors, the MYC gene may be activated by amplification in its surrounding 5' and/or 3' region in HNSCC.