The course of juvenile-onset systemic lupus erythematosus may vary, from rapid multiorgan involvement to insidious development mimicking different medical conditions. Depressive disorder in adolescents poses considerable diagnostic difficulties due to the natural tendency to lowered mood in this age group. However, it may also be the manifestation of a systemic disease. We present a case of a 16-year-old female patient without any somatic symptoms in whom severe depression resistant to treatment was the preceding symptom of juvenile-onset systemic lupus erythematosus (jSLE). Because of isolated proteinuria and presence of antinuclear antibodies, renal biopsy was performed. Light microscopy showed only findings characteristic for membranous nephropathy. Examination on electron microscopy showed characteristic tubuloreticular inclusions (TRIs) which were crucial for making the diagnosis of systemic lupus erythematosus. The evaluation of renal biopsy specimens by electron microscopy could be a useful diagnostic step to confirm the diagnosis, especially in difficult cases where the criteria for SLE are not fully met. The association of mental symptoms with systemic lupus erythematosus and other autoimmune disorders is well documented. However, the increasing prevalence of depression in children and adolescents poses a risk of delaying the diagnosis of a systemic disease.