Symptoms of leukoencephalopathy led to hospital admission of a 59-year-old woman. In addition, a tumor of unknown nature in the pancreas was identified by abdominal ultrasound and CT scan. Following explorative laparotomy and pancreas tail resection, histopathologic analysis revealed a pancreatic pseudotumor with chronic fibrotic pancreatitis. Systemic lupus erythematosus (SLE) was diagnosed due to the presence of antinuclear antibodies (ANA) in serum, antiphospholipid antibodies, and involvement of the central nervous system. Leukoencephalopathy related to anticardiolipin antibodies in serum is a known but rare manifestation of SLE. The concomitant occurrence of chronic pancreatitis can be caused by the development of SLE-induced vasculitis in the pancreas. Subsequent complications of pancreatitis are responsible for the critical, life-threatening state of these patients and may be prevented by early identification of anticardiolipin antibodies and therapy for SLE.