Background: Tinea versicolor is a superficial fungal infection caused by normal skin flora and treatable by topical and oral anti-fungal medications. Objective: To evaluate the clinical and paraclinical response and to compare possible side-effects of a single oral dose of fluconazole and ketoconazole in treatment of tinea versicolor. Patients and Methods: In this clinical trial, sixty-six definite cases of tinea versicolor were divided in two groups using a simple randomization method. The first group consisted of 33 patients who were treated with a single oral dose of 300mg of fluconazole. The second group also consisted of 33 patients who received ketoconazole 400mg orally as a single dose. The patients were evaluated 2 weeks after treatment for therapeutic and paraclinical responses as well as possible side effects. Results: Clinical and paraclinical responses were 60.6% and 78.7% in the first group (Fluconazole) and 33.3% and 51.5% in the second group (Ketoconazole), respectively (P<0.05): There was no statistical difference as far as side-effects were considered (P>0.05). Conclusion: The therapeutic effect of fluconazole as a single oral dose was more than ketoconazole in the treatment of tinea versicolor.