Mycetoma is a chronic, progressive, and destructive disease primarily caused by actinomycetes. This is a report of 4 cases of actinomycotic mycetomas studied in our hospital during the last five years. The patients included 2 men, 56 and 42 years old, and 2 women, 31 and 52 years old, from Khuzestan province located in the south west of Iran. Clinically all patients presented with mycetoma syndrome (Subcutaneous swelling, sinus tracts and granules) with a duration of 3 to 20 years. The lesions were located on the foot in 3 cases and on the hand in one of them. The diagnosis was based on clinical, histopathological and mycological studies. The etiologic agents were Nocardia spp, sterptomyces spp. and actinomyces spp. and one of cultures was negative. All of them were treated with trimethoprime-sulfamethoxazole (TMP-SMZ) plus streptomycin sulfate for several months. We were able to obtain clinical cure in one case and clinical improvement in 2 cases. Early diagnosis favored an efficient therapy and the most effective therapy was combination of TMP-SMZ with streptomycin sulfate.