Abstract: Background: The gene effect in pathogenesis of Rheumatic Diseases is well known, but the exact mode of transmission is not clear. In this report we present similar diseases occurred in two generations and in siblings. Methods: We overviewed the medical charts of second member of the family, according to the family history of the index patient. Results: Family I: Discoid Lupus was diagnosed in an eight years old girl whose father had the same disease as of the age of 34. Skin biopsy done in both cases, confirmed the diagnosis. Interesting enough, father's sister has had Morphea as of the age of 34. Family II: Discoid Lupus appeared as non scaling erythematous macular rashes in a girl at the age of eight months, confirmed by biopsy when she was four years old. At the age of nine she was admitted to the hospital for migratory polyarthritis and CNS involvement and she died despite of the aggressive therapy. Ten years later, her brother at the age of 9 months developed macular rashes that extended to the whole scalp and body in the following years. Now at the age of 3 1/2, he is improving under treatment. Family III: 3 Patients with Behcet's Disease (BD): A 12 year old male, seen at Behcet's Clinic for conjunctivitis and blurred vision with a history of repeated aphthosis for one year. His elder brother, diagnosed for BD at the age of 17 with a 5 years history of eye involvement plus oral and genital aphthosis. Their father diagnosed at the same time with a history of oral and genital aphthosis for 7 years. Family IV: An 18 year old female presented in Nov 1986 with a 5 year history of systemic sclerosis, with digital pitting and ulcer plus face and upper & lower limb sclerosis. This patient, later developed exertional dyspnea and proteinuria that was treated aggressively. In her follow-up visit she complained of hair fall, anorexia and weight loss. Physical examination revealed malar rash and oral ulcer. Laboratory evaluation showed Leuko-Lymphopenia and positive FANA & LE cell plus anti DNA>100.The patient was diagnosed for overlap syndrome of Systemic Sclerosis and SLE. Her mother, at the age of 46 was presented with a 5 years history of Raynauds, dysphagia and polyarthritis. Physical Examination revealed swelling of wrist, MCPs and PIPs and also digital pitting and sclerosing. Her lab Tests showed positive FANA & LE cell plus anti DNA of 87. Now, after 12 years, she has developed multiple telangiectacia plus multiple digital pitting, skin sclerosis and swan neck deformity.