During a 10 year periods, 42 patients with well-documented Midline Malignant Reticulosis were treated with local irradiation and followed for extended periods of time. 13 cases with systemic manifestation after irradiation illustrate the protean features of this disease. Although it commonly Presents in upper airway tracts such as nasal cavity and/or septum, soft palate and palatine tonsil, the lesion may be localized as well as diffuse. 2 cases among them showed systemic relapse on lung, pancreas and scrotum probably from either a multifocal or metastatic deposits. Another 3 eases were associated with systemic diseases such as stomach carcinoma, typhoid enteritis and CNI of fat tissue. Remained cases were diagnosed by clinical or radiological examination. Possibility of close relation to lymphoma with Midline Malignant Reticulosis are also suggested in 1 case. In Midline Malignant Reticulosis, the best results of treatment are obtained in localized lesion of the upper airway treated early with irradiation: A poorer outcome is associated with multifocal systemic involvement, which necessitates a systemic therapy.