The objective of this article is to identify common and atypical features of systemic lupus erythematosus diagnosed following hepatitis B vaccination. We analyzed retrospectively the medical records of 10 systemic lupus erythematosus patients from different centers, who developed the disease following hepatitis B vaccination and determined the prevalence of different manifestations and the time association to vaccination. In this case series, 80% of the patients were female, mean age 35 +/- 9 years, of which 20% received one inoculation, 20% received two doses and 60% received all three inoculations. The mean latency period from the first hepatitis B virus immunization and onset of autoimmune symptoms was 56.3 days. All patients were diagnosed with systemic lupus erythematosus, according to the American College of Rheumatology revised criteria within 1 year. The prevalence of some systemic lupus erythematosus manifestations was typical and included involvement of the joints (100%), skin (80%), muscles (60%) and photosensitivity (30%). Other symptoms differed in this unique group of systemic lupus erythematosus patients such as low rate of kidney and hematologic involvement, and a relatively high rate of hepatitis (20%). Neurological (80%) and pulmonary (70%) symptoms were also common in this group. Data from this case-series, and previously documented cases in the literature could only show a temporal relation between hepatitis B vaccination and the appearance of systemic lupus erythematosus. Systemic lupus erythematosus related to vaccine may differ from idiopathic systemic lupus erythematosus in its clinical presentation and may resemble drug-induced systemic lupus erythematosus. Thus, physicians should be alerted to this potential association, its possible long latency period and unique presentations, and be encouraged to report and analyze these cases.