Background: Non melanoma skin cancer (NMSC) is the most common cancer worldwide. In most cases, the general outlook is excellent; however, local recurrence or metastasis can occur. In this study, we investigated possible tumor and host characteristics affecting the treatment outcome in our department of radiation oncology.Method: We retrospectively studied cases with non melanoma skin cancer (NMSC) who were consecutively referred to department of radiation oncology in Omid and Ghaem Hospitals between 1997 and 2007. The effect of the patients’ characteristics (age, sex), tumor characteristics (histology, size, location), and treatment modalities on prognosis were evaluated.Result: We studies 426 patients with a median age of 65 (range: 14 to 102) and a male to female ratio of 1.4:1. Pathologic review showed 72% of the patients had basal cell carcinoma (BCC) and 28% had squamous cell carcinoma (SCC) with a 5-year event free survival of 87±3% and 67±8%, respectively (p < 0.001). The local recurrence rate was higher in cases with scalp lesions (35%). The patients who underwent combined modality treatment experienced significantly more instances of failure as compared to those receiving radiotherapy alone (5-year event free survival of 81±6% vs. 84±6%, p=0.04) which reflects the higher number of cases with adverse features including larger lesions and/or a positive surgical margin in this group. Sex, age, and multifocality were not significant predictors of prognosis.Conclusion: SCC histology and scalp location were predictive of higher rates of treatment failure in patients with NMSC. There was no correlation between age, sex, multifocality and overall outcome. The higher rate of recurrence in cases receiving combined modality treatment is most probably due to the high number of tumors with adverse prognostic features in these cases.