Background: Squamous cell carcinoma (SCC) is a fatal cancer with world wide spread. Studies concerning the association of viruses specially human papilloma virus with the disease indicate contradictory results. Thus, this study was carried out to investigate the relation between human papilloma virus (HPV) and squamous cell cancer (SCC) in biopsied samples of patients in Zanjan within 2002-2003. Materials and Methods: This case - control study was carried out on biopsied esophageal samples of 34 patients over 25 years of age (17 cases and 17 controls). Biopsied samples were stained through hematoxylin and eosin methods and tested for SCC by light microscope on the basis of cytology (Presence of degenerated cells, vacuolated cell, ...) and histology (HPV). The data were analyzed through Spss software and test. Results: Of 17 patients suffering from SCC 11 people (64.7%) and out of 17 patients without SCC 13 people (76.4%) were effected by HPV indicating no significant relation. Besides, there was no significant relation between HPV and tumor location or cancer differentiation. Conclusion: We did not find a significant relation between HPV and SCC. Regarding the small sample size of the study, sensitivity and specificity of cytopathology method, further studies with more accurate techniques, like chromosome survey, cytogenetic and PCR are recommended.