Abstract: Introduction: Despite the well-established association of malignancy and autoimmune diseases, malignancy seems to be infrequent in Behcet's Disease (BD). The evidence for neoplasm in BD is derived primarily from case reports (only 19 cases in the literature). This study was designed to find the occurrence of malignant disorders in a large group of patients with BD, and their characteristics. Patients & Methods: We reviewed the medical records of all patients with BD, registered at our BD unit during the past 25 years (between 1975 and November 1999), to determine the occurrence of malignancy. The type of the malignancy, and their relationship to different characteristics of the disease, or the treatment regimens as possible risk factors, were specified. Results: Ten out of 4130 cases of BD were complicated with malignant diseases. The different types were as follow: Transitional cell carcinoma of the bladder in 2 cases; ovarian cancer in 2; chronic myeloid leukemia, non-Hodgkin's lymphoma, Kaposi's sarcoma, seminoma of the testis, basal cell carcinoma (BCC) of the skin, and papillary carcinoma of the thyroid each in 1 case. Five were male. When cancer was diagnosed, the age of the patients were between 17 to 69 yr. (Mean: 34.3+15.3). All malignancies occurred after the onset of BD with a range of 1 to 25 years (Mean: 8.5+7.9). The mean age of the onset of BD in them was 25.6+8.9 years with no significant difference with the other BD patients (p=0.9). All the patients had oral aphthosis and skin lesions, 9 had Genital aphthosis, 7 had ocular lesions, 6 had joint involvement, 3 had gastrointestinal manifestations, and 1 had epididymitis. HLAB5 was positive in 4, and Pathergy test in 7 cases. Five of them had received cytotoxic drugs: Four of them oral Cyclophosphamide (those with cancer of the bladder, thyroid, and testis), and one had received Methotrexate (Kaposi's sarcoma). Conclusion: Malignancy is rarely associated with BD in Iranian patients. It was seen only in 0.24% of our cases. The type of these malignancies was rather different from the other reports. We have encountered some types not reported previously such as lymphoma, Kaposi's sarcoma, seminoma, and ovarian, thyroid and skin cancers. Hematopoietic malignancies were rare in our patients. Their occurrence was not related to any of the disease characteristics, or the treatment except for the known relation of bladder cancer to oral Cyclophosphamide, or Kaposi's sarcoma to the immune deficiency due to cytotoxic drugs such as Methotrexate. It is important to emphasize that no cancer was seen after Pulse Cyclophosphamide (4164 pulses).