Breast cancer (BC) is frequent among women in worldwide as well as in India. Several studies have reported a wide variation (1.6-86.2%) in the frequency of incidence of human papillomavirus (HPV) infection in BC with high prevalence of high risk HPV16 subtype. HPV infection in breast can occur through different routes like body fluid or by micro-lesion of breast skin from genital/agential sites, though the actual mode of HPV transmission is not yet known in details. Frequent integration and sequence variation with low copy number of HPV16 were seen in this tumour. In addition, high frequencies of methylation in p97 promoter region of HPV16 were evident in this tumour. Novel splice variants of E6/E7 along with other common variants and their protein expression were seen in the tumour. This indicates the importance of HPV in this tumor, its early diagnosis and prognosis. Thus, HPV may be targeted through vaccination to control the disease. However, detailed analysis of HPV associated molecular pathogenesis of BC is warranted for proper therapeutic intervention.