BACKGROUND Multifocal superficial thrombophlebitis is a rare clinical manifestation with wide differential diagnosis in relation to the background disease. CASE REPORT Here we report on 2 patients who presented with a systemic inflammatory response, multifocal thrombophlebitis, and orbital inflammation in whom a diagnosis of a defined background disease could not be established. CONCLUSIONS The clinical pattern of our 2 cases might represent a distinctive, not yet defined systemic medical condition.