Background: Mycosis fungoides is the most common type of primary cutaneous T-cell lymphoma. Its etiopathogenesis, despite numerous studies, remains unclear. Environmental, viral, and genetic factors have been proposed as its potential etiologic factors. In recent years, viral agents of herpes virus family such as human herpes virus 8 (HHV-8) have been noticed.Objective: The aim of this study was to evaluate the association between the presence of HHV-8 and mycosis fungoides.Methods: This case-control study was done on skin biopsies of 42 mycosis fungoides cases referred to the Department of Pathology, Imam Reza Hospital, Mashhad, Iran from 2004 to2012, and 42 age and sex matched samples of melanocytic nevi. PCR was performed to detect HHV-8 in biopsy samples of the patients and the control group. Statistical analysis was done using the IBM SPSS Statistics (IBM Corp., Armonk, NY, USA) 20.Results: Of 42 patients with MF, 25 were male and 17 were female with a male to female ratio of 1.4. The mean age of the patients was 51.2 years. Most of the patients were in the age group over 60 years. Clinical lesions of the majority of the patients were papules and plaques. HHV-8 DNA was not found in any of the mycosis fungoides samples using the PCR method.Conclusion: Based on our study results, HHV-8 does not play an important role in the pathogenesis of mycosis fungoides.