In this study, the alterations (amplification/rearrangement) of 3 D-type cyclins loci were analyzed by Southern blot in 5 dysplastic head and neck lesions and 79 primary head and neck squamous cell carcinoma (HNSCC) of Indian patients to understand the role of the cyclins in development of the disease. No alteration was found in the dysplastic lesions. Overall, 54% of alterations were found in bcl-1/CCND1 locus, whereas amplification was only found in CCND2 and CCND3 loci in 12% and 2% samples, respectively. In bcl-1/CCND1 locus amplification was the major type of alteration; however, rearrangement as well as coalterations had been seen in some samples indicating the common mechanism of activation of this locus in different types of tumors. In bcl-1 region, the breakpoint clustered in the MTC (major translocation cluster) region, whereas in CCND1 the breakpoint located near 3' end of the gene. The coamplification of CCND2 locus with bcl-1, bcl-1/CCND1, and CNND3 loci suggests cumulative effect of these genes in this tumor. The significant association was seen between bcl-1/CCND1 locus alteration with HPV prevalence and poor patient outcome indicating its importance as prognostic marker. This indicates that the genetic instability caused due to HPV infection may induce the alterations in the bcl-1/CCND1 locus, which will provide selective growth advantage to the specific malignant clones resulting poor prognosis of the disease.