Multisystem inflammatory syndrome in children (MIS-C) is a serious disease with different and various clinical presentations. We may define it as a “game changer” syndrome. Individual clinical entity is seen in each patient and challenge clinicians. We have seen that patients with perforated appendicitis findings on physical examinations who may require urgent surgery recover with steroids or immunomodulators. Treatment must be tailored to each patient individually. Here, we will present three children with a diagnosis of MIS-C who have hemophagocytosis in bone marrow aspiration, which are clinically suggestive of secondary hemophagocytic lympho-histiocytosis (HLH).