Background:Basal cell carcinoma (BCC) is the most common skin cancer among Caucasians, and in most cases, occurs in the sun-exposed areas. In recent years, in addition to many other etiologies such as exposure to UV radiation, and occasionally xeroderma pigmentosa, burns, tattoos, and pox scars, human papillomavirus (HPV) is also considered to have an etiologic role. Different studies were conducted with varied results in this regard.Aims:We evaluate this plausible relationship between HPV and BCC by means of immunohistochemistry (IHC) staining method.Methods:This is an analytic cross-sectional study in which 160 samples were selected randomly consisting of 80 BCC lesions and 80 safe margins. Sampling was done among paraffin-embedded blocks in pathology ward of Kashani and Alzahra hospitals, Isfahan-Iran, from 2004-2007. A section of each block was IHC stained for HPV immunoreactivity (DAKO, Denmark). This was followed by microscopic evaluation in terms of being positive or negative.Results:Fifty seven point five percent of the samples belonged to men and the others to women. In 10%, HPV marker was positive, both in lesion and margin. In 83.8% neither the lesions nor the margins were immunoreactive for HPV. Only in 5 cases (6.3%) the lesion was positive and the margin was negative for this marker. There was no case of immunoreactivity for HPV marker in margins, while it was negative in lesions. Our study results followed by McNemar analysis did not show a significant relationship between BCC incidence and HPV existence. This was consistent in both genders (P > 0.05, power > 90%).Conclusion:In this study we did not find a significant relationship between BCC and HPV, but based on review of articles it appears that large multicentric studies are to be conducted in this regard.